Table of Contents
ISRN Oncology
Volume 2012, Article ID 278093, 23 pages
http://dx.doi.org/10.5402/2012/278093
Review Article

Immunotherapy of Malignant Disease Using Chimeric Antigen Receptor Engrafted T Cells

John Maher1,2,3

1CAR Mechanics Group, Department of Research Oncology, King’s Health Partners Integrated Cancer Centre, King’s College London, Guy’s Hospital Campus, Great Maze Pond, London SE1 9RT, UK
2Department of Immunology, Barnet and Chase Farm Hospitals NHS Trust, Barnet, Hertfordshire EN5 3DJ, UK
3Department of Clinical Immunology and Allergy, King’s College Hospital NHS Foundation Trust, Denmark Hill, London SE5 9RS, UK

Received 23 October 2012; Accepted 14 November 2012

Academic Editors: D. E. Bassi and J. Tovari

Copyright © 2012 John Maher. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. K. Töpfer, S. Kempe, N. Müller et al., “Tumor evasion from T cell surveillance,” Journal of Biomedicine and Biotechnology, vol. 2011, Article ID 918471, 2011. View at Publisher · View at Google Scholar
  2. J. Landsberg, J. Kohlmeyer, M. Renn et al., “Melanomas resist T-cell therapy through inflammation-induced reversible dedifferentiation,” Nature, vol. 490, no. 7420, pp. 412–416, 2012. View at Publisher · View at Google Scholar
  3. S. A. Rosenberg, J. C. Yang, and N. P. Restifo, “Cancer immunotherapy: moving beyond current vaccines,” Nature Medicine, vol. 10, no. 9, pp. 909–915, 2004. View at Publisher · View at Google Scholar · View at Scopus
  4. R. A. Willemsen, C. Ronteltap, P. Chames, R. Debets, and R. L. H. Bolhuis, “T cell retargeting with MHC class I-restricted antibodies: the CD28 costimulatory domain enhances antigen-specific cytotoxicity and cytokine production,” Journal of Immunology, vol. 174, no. 12, pp. 7853–7858, 2005. View at Google Scholar · View at Scopus
  5. G. Stewart-Jones, A. Wadle, A. Hombach et al., “Rational development of high-affinity T-cell receptor-like antibodies,” Proceedings of the National Academy of Sciences of the United States of America, vol. 106, no. 14, pp. 5784–5788, 2009. View at Publisher · View at Google Scholar · View at Scopus
  6. D. V. Tassev, M. Cheng, and N.-K. Cheung, “Retargeting NK92 cells using an HLA-A2-restricted, EBNA3C-specific chimeric antigen receptor,” Cancer Gene Therapy, vol. 19, no. 2, pp. 84–100, 2012. View at Publisher · View at Google Scholar
  7. Y. Kuwana, Y. Asakura, N. Utsunomiya et al., “Expression of chimeric receptor composed of immunoglobulin-derived V regions and T-cell receptor-derived C regions,” Biochemical and Biophysical Research Communications, vol. 149, no. 3, pp. 960–968, 1987. View at Google Scholar · View at Scopus
  8. G. Gross, G. Gorochov, T. Waks, and Z. Eshhar, “Generation of effector T cells expressing chimeric T cell receptor with antibody type-specificity,” Transplantation Proceedings, vol. 21, no. 1 I, pp. 127–130, 1989. View at Google Scholar · View at Scopus
  9. G. Gross, T. Waks, and Z. Eshhar, “Expression of immunoglobulin-T-cell receptor chimeric molecules as functional receptors with antibody-type specificity,” Proceedings of the National Academy of Sciences of the United States of America, vol. 86, no. 24, pp. 10024–10028, 1989. View at Publisher · View at Google Scholar · View at Scopus
  10. Z. Eshhar, T. Waks, G. Gross, and D. G. Schindler, “Specific activation and targeting of cytotoxic lymphocytes through chimeric single chains consisting of antibody-binding domains and the γ or ζ subunits of the immunoglobulin and T-cell receptors,” Proceedings of the National Academy of Sciences of the United States of America, vol. 90, no. 2, pp. 720–724, 1993. View at Publisher · View at Google Scholar · View at Scopus
  11. U. Altenschmidt, R. Kahl, D. Moritz et al., “Cytolysis of tumor cells expressing the Neu/erbB-2, erbB-3, and erbB-4 receptors by genetically targeted naive T lymphocytes,” Clinical Cancer Research, vol. 2, no. 6, pp. 1001–1008, 1996. View at Google Scholar · View at Scopus
  12. A. Muniappan, B. Banapour, J. Lebkowski, and S. Talib, “Ligand-mediated cytolysis of tumor cells: use of heregulin-ζ chimeras to redirect cytotoxic T lymphocytes,” Cancer Gene Therapy, vol. 7, no. 1, pp. 128–134, 2000. View at Google Scholar · View at Scopus
  13. C. R. J. Pameijer, A. Navanjo, B. Meechoovet et al., “Conversion of a tumor-binding peptide identified by phage display to a functional chimeric T cell antigen receptor,” Cancer Gene Therapy, vol. 14, no. 1, pp. 91–97, 2007. View at Publisher · View at Google Scholar · View at Scopus
  14. D. M. Davies, J. Foster, S. J. C. van der Stegen et al., “Flexible targeting of ErbB dimers that drive tumorigenesis by using genetically engineered T cells,” Molecular Medicine, vol. 18, no. 4, pp. 565–576, 2012. View at Publisher · View at Google Scholar
  15. J. Scholler, T. L. Brady, G. Binder-Scholl et al., “Decade-long safety and function of retroviral-modified chimeric antigen receptor T cells,” Science Translational Medicine, vol. 4, no. 132, Article ID 132ra53, 2012. View at Publisher · View at Google Scholar
  16. T. Zhang, M.-R. Wu, and C. L. Sentman, “An NKp30-based chimeric antigen receptor promotes T cell effector functions and antitumor efficacy in vivo,” Journal of Immunology, vol. 189, no. 5, pp. 2290–2299, 2012. View at Publisher · View at Google Scholar
  17. Z. Sharifzadeh, F. Rahbarizadeh, M. A. Shokrgozar et al., “Genetically engineered T cells bearing chimeric nanoconstructed receptors harboring TAG-72-specific camelid single domain antibodies as targeting agents,” Cancer Letters. In press. View at Publisher · View at Google Scholar
  18. K. Urbanska, E. Lanitis, M. Poussin et al., “A universal strategy for adoptive immunotherapy of cancer through use of a novel T-cell antigen receptor,” Cancer Research, vol. 72, no. 7, pp. 1844–1852, 2012. View at Publisher · View at Google Scholar
  19. S. O. Ang, C. Hartline, T. Mi et al., “Generating a chimeric antigen receptor to redirect T-cell specificity after infusion,” Molecular Therapy, vol. 19, no. S137, abstract 353, 2011. View at Google Scholar
  20. K. Tamada, D. Geng, Y. Sakoda, N. Bansal, R. Srivastava, and E. Davila, “Redirecting gene-modified T cells toward various cancer types using tagged antibodies,” Clinical Cancer Research. In press.
  21. M. Chmielewski, A. Hombach, C. Heuser, G. P. Adams, and H. Abken, “T cell activation by antibody-like immunoreceptors: increase in affinity of the single-chain fragment domain above threshold does not increase T cell activation against antigen-positive target cells but decreases selectivity,” Journal of Immunology, vol. 173, no. 12, pp. 7647–7653, 2004. View at Google Scholar · View at Scopus
  22. S. Wilkie, G. Picco, J. Foster et al., “Retargeting of human T cells to tumor-associated MUC1: the evolution of a chimeric antigen receptor,” Journal of Immunology, vol. 180, no. 7, pp. 4901–4909, 2008. View at Google Scholar · View at Scopus
  23. M. H. Kershaw, J. A. Westwood, L. L. Parker et al., “A phase I study on adoptive immunotherapy using gene-modified T cells for ovarian cancer,” Clinical Cancer Research, vol. 12, no. 20, pp. 6106–6115, 2006. View at Publisher · View at Google Scholar · View at Scopus
  24. C. H. J. Lamers, R. Willemsen, P. Van Elzakker et al., “Immune responses to transgene and retroviral vector in patients treated with ex vivo-engineered T cells,” Blood, vol. 117, no. 1, pp. 72–82, 2011. View at Publisher · View at Google Scholar · View at Scopus
  25. D. Moritz and B. Groner, “A spacer region between the single chain antibody-and the CDS ζ-chain domain of chimeric T cell receptor components is required for efficient ligand binding and signaling activity,” Gene Therapy, vol. 2, no. 8, pp. 539–546, 1995. View at Google Scholar · View at Scopus
  26. R. D. Guest, R. E. Hawkins, N. Kirillova et al., “The role of extracellular spacer regions in the optimal design of chimeric immune receptors: evaluation of four different scFvs and antigens,” Journal of Immunotherapy, vol. 28, no. 3, pp. 203–211, 2005. View at Google Scholar · View at Scopus
  27. S. E. James, P. D. Greenberg, M. C. Jensen et al., “Antigen sensitivity of CD22-specific chimeric TCR is modulated by target epitope distance from the cell membrane,” Journal of Immunology, vol. 180, no. 10, pp. 7028–7038, 2008. View at Google Scholar · View at Scopus
  28. A. Hombach, A. A. Hombach, and H. Abken, “Adoptive immunotherapy with genetically engineered T cells: modification of the IgG1 Fc spacer domain in the extracellular moiety of chimeric antigen receptors avoids off-target activation and unintended initiation of an innate immune response,” Gene Therapy, vol. 17, no. 10, pp. 1206–1213, 2010. View at Publisher · View at Google Scholar · View at Scopus
  29. J. S. Bridgeman, R. E. Hawkins, S. Bagley, M. Blaylock, M. Holland, and D. E. Gilham, “The optimal antigen response of chimeric antigen receptors harboring the CD3ζ transmembrane domain is dependent upon incorporation of the receptor into the endogenous TCR/CD3 complex,” Journal of Immunology, vol. 184, no. 12, pp. 6938–6949, 2010. View at Publisher · View at Google Scholar · View at Scopus
  30. B. A. Irving and A. Weiss, “The cytoplasmic domain of the T cell receptor ζ chain is sufficient to couple to receptor-associated signal transduction pathways,” Cell, vol. 64, no. 5, pp. 891–901, 1991. View at Google Scholar · View at Scopus
  31. N. M. Haynes, M. B. Snook, J. A. Trapani et al., “Redirecting mouse CTL against colon carcinoma: superior signaling efficacy of single-chain variable domain chimeras containing TCR-ζ vs FcεRI-γ,” Journal of Immunology, vol. 166, no. 1, pp. 182–187, 2001. View at Google Scholar · View at Scopus
  32. A. Krause, H. F. Guo, J. B. Latouche, C. Tan, N. K. V. Cheung, and M. Sadelain, “Antigen-dependent CD28 signaling selectively enhances survival and proliferation in genetically modified activated human primary T lymphocytes,” Journal of Experimental Medicine, vol. 188, no. 4, pp. 619–626, 1998. View at Publisher · View at Google Scholar · View at Scopus
  33. H. M. Finney, A. D. G. Lawson, C. R. Bebbington, and A. N. C. Weir, “Chimeric receptors providing both primary and costimulatory signaling in T cells from a single gene product,” Journal of Immunology, vol. 161, no. 6, pp. 2791–2797, 1998. View at Google Scholar · View at Scopus
  34. J. Maher, R. J. Brentjens, G. Gunset, I. Rivière, and M. Sadelain, “Human T-lymphocyte cytotoxicity and proliferation directed by a single chimeric TCRζ/CD28 receptor,” Nature Biotechnology, vol. 20, no. 1, pp. 70–75, 2002. View at Publisher · View at Google Scholar · View at Scopus
  35. N. M. Haynes, J. A. Trapani, M. W. L. Teng et al., “Single-chain antigen recognition receptors that costimulate potent rejection of established experimental tumors,” Blood, vol. 100, no. 9, pp. 3155–3163, 2002. View at Publisher · View at Google Scholar
  36. N. M. Haynes, J. A. Trapani, M. W. L. Teng et al., “Rejection of syngeneic colon carcinoma by CTLs expressing single-chain antibody receptors codelivering CD28 costimulation,” Journal of Immunology, vol. 169, no. 10, pp. 5780–5786, 2002. View at Google Scholar
  37. C. Carpenito, M. C. Milone, R. Hassan et al., “Control of large, established tumor xenografts with genetically retargeted human T cells containing CD28 and CD137 domains,” Proceedings of the National Academy of Sciences of the United States of America, vol. 106, no. 9, pp. 3360–3365, 2009. View at Publisher · View at Google Scholar · View at Scopus
  38. H. M. Finney, A. N. Akbar, and A. D. G. Lawson, “Activation of resting human primary T cells with chimeric receptors: costimulation from CD28, inducible costimulator, CD134, and CD137 in series with signals from the TCRζ chain,” Journal of Immunology, vol. 172, no. 1, pp. 104–113, 2004. View at Google Scholar · View at Scopus
  39. R. J. Brentjens, E. Santos, Y. Nikhamin et al., “Genetically targeted T cells eradicate systemic acute lymphoblastic leukemia xenografts,” Clinical Cancer Research, vol. 13, no. 18, pp. 5426–5435, 2007. View at Publisher · View at Google Scholar · View at Scopus
  40. C. Imai, K. Mihara, M. Andreansky et al., “Chimeric receptors with 4-1BB signaling capacity provoke potent cytotoxicity against acute lymphoblastic leukemia,” Leukemia, vol. 18, no. 4, pp. 676–684, 2004. View at Publisher · View at Google Scholar · View at Scopus
  41. D.-G. Song, Q. Ye, M. Poussin, G. M. Harms, M. Figini, and D. J. Powell Jr., “CD27 costimulation augments the survival and antitumor activity of redirected human T cells in vivo,” Blood, vol. 119, no. 3, pp. 696–706, 2012. View at Publisher · View at Google Scholar
  42. B. Altvater, S. Landmeier, S. Pscherer et al., “2B4 (CD244) signaling via chimeric receptors costimulates tumor-antigen specific proliferation and in vitro expansion of human T cells,” Cancer Immunology, Immunotherapy, vol. 58, no. 12, pp. 1991–2001, 2009. View at Publisher · View at Google Scholar · View at Scopus
  43. S. Guedan, C. Carpenito, and S. E. McGettigan, “Redirection of TH17 cells with a CAR containing the ICOS costimulatory domain enhances function, antitumor Activity and persistence of TH17 cells,” Molecular Therapy, vol. 20, no. S130, abstract 329, 2012. View at Google Scholar
  44. A. Loskog, V. Giandomenico, C. Rossig, M. Pule, G. Dotti, and M. K. Brenner, “Addition of the CD28 signaling domain to chimeric T-cell receptors enhances chimeric T-cell resistance to T regulatory cells,” Leukemia, vol. 20, no. 10, pp. 1819–1828, 2006. View at Publisher · View at Google Scholar · View at Scopus
  45. H. Koehler, D. Kofler, A. Hombach, and H. Abken, “CD28 costimulation overcomes transforming growth factor-β-mediated repression of proliferation of redirected human CD4+ and CD8+ T cells in an antitumor cell attack,” Cancer Research, vol. 67, no. 5, pp. 2265–2273, 2007. View at Publisher · View at Google Scholar · View at Scopus
  46. D. M. Kofler, M. Chmielewski, G. Rappl et al., “CD28 costimulation impairs the efficacy of a redirected T-cell antitumor attack in the presence of regulatory T cells which can be overcome by preventing lck activation,” Molecular Therapy, vol. 19, no. 4, pp. 760–767, 2011. View at Publisher · View at Google Scholar · View at Scopus
  47. M. C. Milone, J. D. Fish, C. Carpenito et al., “Chimeric receptors containing CD137 signal transduction domains mediate enhanced survival of T cells and increased antileukemic efficacy in vivo,” Molecular Therapy, vol. 17, no. 8, pp. 1453–1464, 2009. View at Publisher · View at Google Scholar · View at Scopus
  48. C. M. Kowolik, M. S. Topp, S. Gonzalez et al., “CD28 costimulation provided through a CD19-specific chimeric antigen receptor enhances in vivo persistence and antitumor efficacy of adoptively transferred T cells,” Cancer Research, vol. 66, no. 22, pp. 10995–11004, 2006. View at Publisher · View at Google Scholar · View at Scopus
  49. M. Kalos, B. L. Levine, D. L. Porter et al., “T cells with chimeric antigen receptors have potent antitumor effects and can establish memory in patients with advanced leukemia,” Science Translational Medicine, vol. 3, no. 95, Article ID 95ra73, 2011. View at Publisher · View at Google Scholar
  50. D. L. Porter, B. L. Levine, M. Kalos, A. Bagg, and C. H. June, “Chimeric antigen receptor-modified T cells in chronic lymphoid leukemia,” New England Journal of Medicine, vol. 365, no. 8, pp. 725–733, 2011. View at Publisher · View at Google Scholar
  51. B. Savoldo, C. A. Ramos, E. Liu et al., “CD28 costimulation improves expansion and persistence of chimeric antigen receptor-modified T cells in lymphoma patients,” Journal of Clinical Investigation, vol. 121, no. 5, pp. 1822–1826, 2011. View at Publisher · View at Google Scholar · View at Scopus
  52. S. Wilkie, M. C. I. Van Schalkwyk, S. Hobbs et al., “Dual targeting of ErbB2 and MUC1 in breast cancer using chimeric antigen receptors engineered to provide complementary signaling,” Journal of Clinical Immunology, vol. 32, no. 5, pp. 1059–1070, 2012. View at Publisher · View at Google Scholar
  53. J. Sun, G. Dotti, L. E. Huye et al., “T cells expressing constitutively active Akt resist multiple tumor-associated inhibitory mechanisms,” Molecular Therapy, vol. 18, no. 11, pp. 2006–2017, 2010. View at Publisher · View at Google Scholar · View at Scopus
  54. N. Kunii, Y. Zhao, S. Jiang et al., “Enhanced function of redirected human T cells expressing linker for activation of T-cells that is resistant to ubiquitylation,” Human Gene Therapy. In press.
  55. T. L. Geiger, P. Nguyen, D. Leitenberg, and R. A. Flavell, “Integrated src kinase and costimulatory activity enhances signal transduction through single-chain chimeric receptors in T lymphocytes,” Blood, vol. 98, no. 8, pp. 2364–2371, 2001. View at Publisher · View at Google Scholar · View at Scopus
  56. A. A. Hombach, J. Heiders, M. Foppe, M. Chmielewski, and H. Abken, “OX40 costimulation by a chimeric antigen receptor abrogates CD28 and IL-2 induced IL-10 secretion by redirected CD4+ T cells,” Oncoimmunology, vol. 1, pp. 458–466, 2012. View at Google Scholar
  57. M. A. Pulè, K. C. Straathof, G. Dotti, H. E. Heslop, C. M. Rooney, and M. K. Brenner, “A chimeric T cell antigen receptor that augments cytokine release and supports clonal expansion of primary human T cells,” Molecular Therapy, vol. 12, no. 5, pp. 933–941, 2005. View at Publisher · View at Google Scholar · View at Scopus
  58. X. S. Zhong, M. Matsushita, J. Plotkin, I. Riviere, and M. Sadelain, “Chimeric antigen receptors combining 4-1BB and CD28 signaling domains augment PI3 kinase/AKT/Bcl-XL activation and CD8+ T cell-mediated tumor eradication,” Molecular Therapy, vol. 18, no. 2, pp. 413–420, 2010. View at Publisher · View at Google Scholar · View at Scopus
  59. J. Wang, M. Jensen, Y. Lin et al., “Optimizing adoptive polyclonal T cell immunotherapy of lymphomas, using a chimeric T cell receptor possessing CD28 and CD137 costimulatory domains,” Human Gene Therapy, vol. 18, no. 8, pp. 712–725, 2007. View at Publisher · View at Google Scholar · View at Scopus
  60. M. T. Stephan, V. Ponomarev, R. J. Brentjens et al., “T cell-encoded CD80 and 4-1BBL induce auto- and transcostimulation, resulting in potent tumor rejection,” Nature Medicine, vol. 13, no. 12, pp. 1440–1449, 2007. View at Publisher · View at Google Scholar · View at Scopus
  61. S. P. Zehntner, M. Brisebois, E. Tran, T. Owens, and S. Fournier, “Constitutive expression of a costimulatory ligand on antigen-presenting cells in the nervous system drives demyelinating disease,” FASEB Journal, vol. 17, pp. 1910–1912, 2003. View at Google Scholar
  62. K. Murata, M. Nose, L. C. Ndhlovu, T. Sato, K. Sugamura, and N. Ishii, “Constitutive OX40/OX40 ligand interaction induces autoimmune-like diseases,” Journal of Immunology, vol. 169, no. 8, pp. 4628–4636, 2002. View at Google Scholar · View at Scopus
  63. G. F. Salinas, T. Cantaert, and M. Nolte, “Constitutive co-stimulation by B cells is sufficient to trigger T cell-driven autoimmune disease,” Annals of the Rheumatic Diseases, vol. 69, no. A71, 2010. View at Google Scholar
  64. C. Imai, S. Iwamoto, and D. Campana, “Genetic modification of primary natural killer cells overcomes inhibitory signals and induces specific killing of leukemic cells,” Blood, vol. 106, no. 1, pp. 376–383, 2005. View at Publisher · View at Google Scholar · View at Scopus
  65. B. Altvater, S. Landmeier, S. Pscherer et al., “2B4 (CD244) signaling by recombinant antigen-specific chimeric receptors costimulates natural killer cell activation to leukemia and neuroblastoma cells,” Clinical Cancer Research, vol. 15, no. 15, pp. 4857–4866, 2009. View at Publisher · View at Google Scholar · View at Scopus
  66. C. J. Denman, V. V. Senyukov, S. S. Somanchi et al., “Membrane-bound IL-21 promotes sustained Ex Vivo proliferation of human natural killer cells,” PLoS ONE, vol. 7, no. 1, Article ID e30264, 2012. View at Publisher · View at Google Scholar
  67. N. Lapteva, A. G. Durett, J. Sun et al., “Large-scale ex vivo expansion and characterization of natural killer cells for clinical applications,” Cytotherapy, vol. 14, no. 9, pp. 1131–1143, 2012. View at Publisher · View at Google Scholar
  68. M. Rischer, S. Pscherer, S. Duwe, J. Vormoor, H. Jürgens, and C. Rossig, “Human γδ T cells as mediators of chimaeric-receptor redirected anti-tumour immunity,” British Journal of Haematology, vol. 126, no. 4, pp. 583–592, 2004. View at Publisher · View at Google Scholar · View at Scopus
  69. H. Torikai, A. Reik, P.-Q. Liu et al., “A foundation for universal T-cell based immunotherapy: T cells engineered to express a CD19-specific chimeric-antigen-receptor and eliminate expression of endogenous TCR,” Blood, vol. 119, no. 24, pp. 5697–5705, 2012. View at Publisher · View at Google Scholar
  70. M. E. Dudley, J. R. Wunderlich, P. F. Robbins et al., “Cancer regression and autoimmunity in patients after clonal repopulation with antitumor lymphocytes,” Science, vol. 298, no. 5594, pp. 850–854, 2002. View at Publisher · View at Google Scholar · View at Scopus
  71. M. E. Dudley, J. C. Yang, R. Sherry et al., “Adoptive cell therapy for patients with metastatic melanoma: evaluation of intensive myeloablative chemoradiation preparative regimens,” Journal of Clinical Oncology, vol. 26, no. 32, pp. 5233–5239, 2008. View at Publisher · View at Google Scholar · View at Scopus
  72. A. Barber, A. Rynda, and C. L. Sentman, “Chimeric NKG2D expressing T cells eliminate immunosuppression and activate immunity within the ovarian tumor microenvironment,” Journal of Immunology, vol. 183, no. 11, pp. 6939–6947, 2009. View at Publisher · View at Google Scholar · View at Scopus
  73. P. Spear, A. Barber, A. Rynda-Apple, and C. L. Sentman, “Chimeric antigen receptor T cells shape myeloid cell function within the tumor microenvironment through IFN-γ and GM-CSF,” Journal of Immunology, vol. 188, no. 12, pp. 6389–6398, 2012. View at Publisher · View at Google Scholar
  74. S. P. Kerkar, P. Muranski, A. Kaiser et al., “Tumor-specific CD8+ T cells expressing interleukin-12 eradicate established cancers in lymphodepleted hosts,” Cancer Research, vol. 70, no. 17, pp. 6725–6734, 2010. View at Publisher · View at Google Scholar · View at Scopus
  75. D. Chinnasamy, Z. Yu, S. P. Kerkar et al., “Local delivery of interleukin-12 using T cells targeting VEGF receptor-2 eradicates multiple vascularized tumors in mice,” Clinical Cancer Research, vol. 18, no. 6, pp. 1672–1683, 2012. View at Publisher · View at Google Scholar
  76. H. J. Pegram, J. C. Lee, E. G. Hayman et al., “Tumor-targeted T cells modified to secrete IL-12 eradicate systemic tumors without need for prior conditioning,” Blood, vol. 119, no. 18, pp. 4133–4141, 2012. View at Publisher · View at Google Scholar
  77. M. Chmielewski, C. Kopecky, A. A. Hombach, and H. Abken, “IL-12 release by engineered T cells expressing chimeric antigen receptors can effectively muster an antigen-independent macrophage response on tumor cells that have shut down tumor antigen expression,” Cancer Research, vol. 71, no. 17, pp. 5697–5706, 2011. View at Publisher · View at Google Scholar
  78. S. P. Kerkar, R. S. Goldszmid, P. Muranski et al., “IL-12 triggers a programmatic change in dysfunctional myeloid-derived cells within mouse tumors,” Journal of Clinical Investigation, vol. 121, no. 12, pp. 4746–4757, 2011. View at Publisher · View at Google Scholar
  79. A. C. Parente-Pereira, J. Burnet, D. Ellison et al., “Trafficking of CAR-engineered human T cells following regional or systemic adoptive transfer in SCID beige mice,” Journal of Clinical Immunology, vol. 31, no. 4, pp. 710–718, 2011. View at Publisher · View at Google Scholar · View at Scopus
  80. R. J. Brentjens, I. Rivière, J. H. Park et al., “Safety and persistence of adoptively transferred autologous CD19-targeted T cells in patients with relapsed or chemotherapy refractory B-cell leukemias,” Blood, vol. 118, no. 18, pp. 4817–4828, 2011. View at Publisher · View at Google Scholar
  81. M. H. Kershaw, G. Wang, J. A. Westwood et al., “Redirecting migration of T cells to chemokine secreted from tumors by genetic modification with CXCR2,” Human Gene Therapy, vol. 13, no. 16, pp. 1971–1980, 2002. View at Publisher · View at Google Scholar · View at Scopus
  82. A. Di Stasi, B. De Angelis, C. M. Rooney et al., “T lymphocytes coexpressing CCR4 and a chimeric antigen receptor targeting CD30 have improved homing and antitumor activity in a Hodgkin tumor model,” Blood, vol. 113, no. 25, pp. 6392–6402, 2009. View at Publisher · View at Google Scholar · View at Scopus
  83. E. K. Moon, C. Carpenito, J. Sun et al., “Expression of a functional CCR2 receptor enhances tumor localization and tumor eradication by retargeted human T cells expressing a mesothelin-specific chimeric antibody receptor,” Clinical Cancer Research, vol. 17, no. 14, pp. 4719–4730, 2011. View at Publisher · View at Google Scholar · View at Scopus
  84. A. S. Y. Lo, J. R. Taylor, F. Farzaneh, D. M. Kemeny, N. J. Dibb, and J. Maher, “Harnessing the tumour-derived cytokine, CSF-1, to co-stimulate T-cell growth and activation,” Molecular Immunology, vol. 45, no. 5, pp. 1276–1287, 2008. View at Publisher · View at Google Scholar · View at Scopus
  85. J. H. Pinthus, T. Waks, V. Malina et al., “Adoptive immunotherapy of prostate cancer bone lesions using redirected effector lymphocytes,” Journal of Clinical Investigation, vol. 114, no. 12, pp. 1774–1781, 2004. View at Publisher · View at Google Scholar · View at Scopus
  86. R. Sackstein, J. S. Merzaban, D. W. Cain et al., “Ex vivo glycan engineering of CD44 programs human multipotent mesenchymal stromal cell trafficking to bone,” Nature Medicine, vol. 14, no. 2, pp. 181–187, 2008. View at Publisher · View at Google Scholar · View at Scopus
  87. S. N. Robinson, P. J. Simmons, M. W. Thomas et al., “Ex vivo fucosylation improves human cord blood engraftment in NOD-SCID IL-2Rγnull mice,” Experimental Hematology, vol. 40, no. 6, pp. 445–456, 2012. View at Publisher · View at Google Scholar
  88. R. Brentjens, R. Yeh, Y. Bernal, I. Riviere, and M. Sadelain, “Treatment of chronic lymphocytic leukemia with genetically targeted autologous t cells: case report of an unforeseen adverse event in a phase i clinical trial,” Molecular Therapy, vol. 18, no. 4, pp. 666–668, 2010. View at Publisher · View at Google Scholar · View at Scopus
  89. R. A. Morgan, J. C. Yang, M. Kitano, M. E. Dudley, C. M. Laurencot, and S. A. Rosenberg, “Case report of a serious adverse event following the administration of t cells transduced with a chimeric antigen receptor recognizing ERBB2,” Molecular Therapy, vol. 18, no. 4, pp. 843–851, 2010. View at Publisher · View at Google Scholar · View at Scopus
  90. F. Thistlethwaite, D. Rothwell, A. Byatte et al., “A CRUK phase I trial of adoptive transfer of autologous tumour antigen-specific T cells with pre-conditioning chemotherapy and intravenous IL2 in patients with advanced CEA positive tumours,” UK NCRI Conference, Abstract LB14, 2010, http://www.ncri.org.uk/ncriconference/2010abstracts/abstracts/LB14.htm.
  91. A. Murphy, J. A. Westwood, L. E. Brown et al., “Antitumor activity of dual-specific T cells and influenza virus,” Cancer Gene Therapy, vol. 14, no. 5, pp. 499–508, 2007. View at Publisher · View at Google Scholar · View at Scopus
  92. M. A. Pule, B. Savoldo, G. D. Myers et al., “Virus-specific T cells engineered to coexpress tumor-specific receptors: persistence and antitumor activity in individuals with neuroblastoma,” Nature Medicine, vol. 14, no. 11, pp. 1264–1270, 2008. View at Publisher · View at Google Scholar · View at Scopus
  93. S. Terakura, T. N. Yamamoto, R. A. Gardner, C. J. Turtle, M. C. Jensen, and S. R. Riddell, “Generation of CD19-chimeric antigen receptor modified CD8+ T cells derived from virus-specific central memory T cells,” Blood, vol. 119, no. 1, pp. 72–82, 2012. View at Publisher · View at Google Scholar
  94. A. Dutour, V. Marin, I. Pizzitola et al., “In vitro and in vivo antitumor effect of anti-CD33 chimeric receptor-expressing EBV-CTL against CD 33+ acute myeloid leukemia,” Advances in Hematology, vol. 2012, Article ID 683065, 2012. View at Publisher · View at Google Scholar
  95. C. Rossig, A. Bär, S. Pscherer et al., “Target antigen expression on a professional antigen-presenting cell induces superior proliferative antitumor T-cell responses via chimeric T-cell receptors,” Journal of Immunotherapy, vol. 29, no. 1, pp. 21–31, 2006. View at Publisher · View at Google Scholar · View at Scopus
  96. K. P. Micklethwaite, B. Savoldo, P. J. Hanley et al., “Derivation of human T lymphocytes from cord blood and peripheral blood with antiviral and antileukemic specificity from a single culture as protection against infection and relapse after stem cell transplantation,” Blood, vol. 115, no. 13, pp. 2695–2703, 2010. View at Publisher · View at Google Scholar · View at Scopus
  97. B. G. Till, M. C. Jensen, J. Wang et al., “Adoptive immunotherapy for indolent non-hodgkin lymphoma and mantle cell lymphoma using genetically modified autologous CD20-specific T cells,” Blood, vol. 112, no. 6, pp. 2261–2271, 2008. View at Publisher · View at Google Scholar · View at Scopus
  98. M. T. Lotze, W. J. Buchser, and X. Liang, “Blocking the interleukin 2 (IL2)-induced systemic autophagic syndrome promotes profound antitumor effects and limits toxicity,” Autophagy, vol. 8, no. 8, pp. 1264–1266, 2012. View at Publisher · View at Google Scholar
  99. C. Quintarelli, J. F. Vera, B. Savoldo et al., “Co-expression of cytokine and suicide genes to enhance the activity and safety of tumor-specific cytotoxic T lymphocytes,” Blood, vol. 110, no. 8, pp. 2793–2802, 2007. View at Publisher · View at Google Scholar · View at Scopus
  100. B. Heemskerk, K. Liu, M. E. Dudley et al., “Adoptive cell therapy for patients with melanoma, using tumor-infiltrating lymphocytes genetically engineered to secrete interleukin-2,” Human Gene Therapy, vol. 19, no. 5, pp. 496–510, 2008. View at Publisher · View at Google Scholar · View at Scopus
  101. L. S. Evans, P. R. Witte, A. L. Feldbaus et al., “Expression of chimeric granulocyte-macrophage colony-stimulating factor/interleukin 2 receptors in human cytotoxic T lymphocyte clones results in granulocyte-macrophage colony-stimulating factor-dependent growth,” Human Gene Therapy, vol. 10, no. 12, pp. 1941–1951, 1999. View at Publisher · View at Google Scholar · View at Scopus
  102. J. F. Vera, V. Hoyos, B. Savoldo et al., “Genetic manipulation of tumor-specific cytotoxic T lymphocytes to restore responsiveness to IL-7,” Molecular Therapy, vol. 17, no. 5, pp. 880–888, 2009. View at Publisher · View at Google Scholar · View at Scopus
  103. S. Wilkie, S. E. Burbridge, L. Chiapero-Stanke et al., “Selective expansion of chimeric antigen receptor-targeted T-cells with potent effector function using interleukin-4,” Journal of Biological Chemistry, vol. 285, no. 33, pp. 25538–25544, 2010. View at Publisher · View at Google Scholar · View at Scopus
  104. R. Goldstein, C. Hanley, J. Morris et al., “Clinical investigation of the role of interleukin-4 and interleukin-13 in the evolution of prostate cancer,” Cancers, vol. 3, no. 4, pp. 4281–4293, 2011. View at Publisher · View at Google Scholar
  105. H. Singh, L. M. Serrano, T. Pfeiffer et al., “Combining adoptive cellular and immunocytokine therapies to improve treatment of B-lineage malignancy,” Cancer Research, vol. 67, no. 6, pp. 2872–2880, 2007. View at Publisher · View at Google Scholar · View at Scopus
  106. L. Gattinoni, C. A. Klebanoff, and N. P. Restifo, “Paths to stemness: building the ultimate antitumour T cell,” Nature Reviews Cancer, vol. 12, no. 10, pp. 671–684, 2012. View at Publisher · View at Google Scholar
  107. Z. Li, J. Düllmann, B. Schiedlmeier et al., “Murine leukemia induced by retroviral gene marking,” Science, vol. 296, no. 5567, p. 497, 2002. View at Publisher · View at Google Scholar · View at Scopus
  108. M. G. Ott, M. Schmidt, K. Schwarzwaelder et al., “Correction of X-linked chronic granulomatous disease by gene therapy, augmented by insertional activation of MDS1-EVI1, PRDM16 or SETBP1,” Nature Medicine, vol. 12, no. 4, pp. 401–409, 2006. View at Publisher · View at Google Scholar · View at Scopus
  109. S. Stein, M. G. Ott, S. Schultze-Strasser et al., “Genomic instability and myelodysplasia with monosomy 7 consequent to EVI1 activation after gene therapy for chronic granulomatous disease,” Nature Medicine, vol. 16, no. 2, pp. 198–204, 2010. View at Publisher · View at Google Scholar · View at Scopus
  110. S. Newrzela, K. Cornils, T. Heinrich et al., “Retroviral insertional mutagenesis can contribute to immortalization of mature T lymphocytes,” Molecular Medicine, vol. 17, no. 11, pp. 1223–1232, 2011. View at Publisher · View at Google Scholar
  111. C. Traversari, S. Marktel, Z. Magnani et al., “The potential immunogenicity of the TK suicide gene does not prevent full clinical benefit associated with the use of TK-transduced donor lymphocytes in HSCT for hematologic malignancies,” Blood, vol. 109, no. 11, pp. 4708–4715, 2007. View at Publisher · View at Google Scholar · View at Scopus
  112. A. Recchia, C. Bonini, Z. Magnani et al., “Retroviral vector integration deregulates gene expression but has no consequence on the biology and function of transplanted T cells,” Proceedings of the National Academy of Sciences of the United States of America, vol. 103, no. 5, pp. 1457–1462, 2006. View at Publisher · View at Google Scholar · View at Scopus
  113. C. Bonini, A. Bondanza, S. K. Perna et al., “The suicide gene therapy challenge: how to improve a successful gene therapy approach,” Molecular Therapy, vol. 15, no. 7, pp. 1248–1252, 2007. View at Publisher · View at Google Scholar · View at Scopus
  114. M. K. Brenner, “Gene transfer and the treatment of haematological malignancy,” Journal of Internal Medicine, vol. 249, no. 4, pp. 345–358, 2001. View at Publisher · View at Google Scholar · View at Scopus
  115. P. Tiberghien, C. Ferrand, B. Lioure et al., “Administration of herpes simplex-thymidine kinase-expressing donor T cells with a T-cell-depleted allogeneic marrow graft,” Blood, vol. 97, no. 1, pp. 63–72, 2001. View at Publisher · View at Google Scholar · View at Scopus
  116. L. M. Muul, L. M. Tuschong, S. L. Soenen et al., “Persistence and expression of the adenosine deaminase gene for 12 years and immune reaction to gene transfer components: long-term results of the first clinical gene therapy trial,” Blood, vol. 101, no. 7, pp. 2563–2569, 2003. View at Publisher · View at Google Scholar · View at Scopus
  117. S. H. Yoon, J. M. Lee, H. I. Cho et al., “Adoptive immunotherapy using human peripheral blood lymphocytes transferred with RNA encoding Her-2neu-specific chimeric immune receptor in ovarian cancer xenograft model,” Cancer Gene Therapy, vol. 16, no. 6, pp. 489–497, 2009. View at Publisher · View at Google Scholar · View at Scopus
  118. Y. Zhao, Z. Zheng, C. J. Cohen et al., “High-efficiency transfection of primary human and mouse T lymphocytes using RNA electroporation,” Molecular Therapy, vol. 13, no. 1, pp. 151–159, 2006. View at Publisher · View at Google Scholar · View at Scopus
  119. D. M. Barrett, Y. Zhao, X. Liu et al., “Treatment of advanced leukemia in mice with mRNA engineered T cells,” Human Gene Therapy, vol. 22, no. 12, pp. 1575–1586, 2011. View at Publisher · View at Google Scholar
  120. Y. Zhao, E. Moon, C. Carpenito et al., “Multiple injections of electroporated autologous T cells expressing a chimeric antigen receptor mediate regression of human disseminated tumor,” Cancer Research, vol. 70, no. 22, pp. 9053–9061, 2010. View at Publisher · View at Google Scholar · View at Scopus
  121. Y. Nakazawa, L. E. Huye, V. S. Salsman et al., “PiggyBac-mediated cancer immunotherapy using EBV-specific cytotoxic T-cells expressing HER2-specific chimeric antigen receptor,” Molecular Therapy, vol. 19, pp. 2133–2143, 2011. View at Publisher · View at Google Scholar · View at Scopus
  122. H. Singh, P. R. Manuri, S. Olivares et al., “Redirecting specificity of T-cell populations for CD19 using the sleeping beauty system,” Cancer Research, vol. 68, no. 8, pp. 2961–2971, 2008. View at Publisher · View at Google Scholar · View at Scopus
  123. D. Hollyman, J. Stefanski, M. Przybylowski et al., “Manufacturing validation of biologically functional T cells targeted to CD19 antigen for autologous adoptive cell therapy,” Journal of Immunotherapy, vol. 32, no. 2, pp. 169–180, 2009. View at Publisher · View at Google Scholar · View at Scopus
  124. M. M. Suhoski, T. N. Golovina, N. A. Aqui et al., “Engineering artificial antigen-presenting cells to express a diverse array of co-stimulatory molecules,” Molecular Therapy, vol. 15, no. 5, pp. 981–988, 2007. View at Publisher · View at Google Scholar · View at Scopus
  125. L. X. J. Wang, J. A. Westwood, M. Moeller et al., “Tumor ablation by gene-modified T cells in the absence of autoimmunity,” Cancer Research, vol. 70, no. 23, pp. 9591–9598, 2010. View at Publisher · View at Google Scholar · View at Scopus
  126. R. Bos, S. Van Duikeren, H. Morreau et al., “Balancing between antitumor efficacy and autoimmune pathology in T-cell-mediated targeting of carcinoembryonic antigen,” Cancer Research, vol. 68, no. 20, pp. 8446–8455, 2008. View at Publisher · View at Google Scholar · View at Scopus
  127. M. R. Parkhurst, J. C. Yang, R. C. Langan et al., “T cells targeting carcinoembryonic antigen can mediate regression of metastatic colorectal cancer but induce severe transient colitis,” Molecular Therapy, vol. 19, no. 3, pp. 620–626, 2011. View at Publisher · View at Google Scholar · View at Scopus
  128. C. Berger, M. E. Flowers, E. H. Warren, and S. R. Riddell, “Analysis of transgene-specific immune responses that limit the in vivo persistence of adoptively transferred HSV-TK-modified donor T cells after allogeneic hematopoietic cell transplantation,” Blood, vol. 107, no. 6, pp. 2294–2302, 2006. View at Publisher · View at Google Scholar · View at Scopus
  129. K. C. Straathof, M. A. Pulè, P. Yotnda et al., “An inducible caspase 9 safety switch for T-cell therapy,” Blood, vol. 105, no. 11, pp. 4247–4254, 2005. View at Publisher · View at Google Scholar · View at Scopus
  130. A. Di Stasi, S.-K. Tey, G. Dotti et al., “Inducible apoptosis as a safety switch for adoptive cell therapy,” New England Journal of Medicine, vol. 365, no. 18, pp. 1673–1683, 2011. View at Publisher · View at Google Scholar
  131. Y. Chu, N. Senghaas, R. W. Köster, W. Wurst, and R. Kühn, “Novel Caspase-suicide proteins for tamoxifen-inducible apoptosis,” Genesis, vol. 46, no. 10, pp. 530–536, 2008. View at Publisher · View at Google Scholar · View at Scopus
  132. B. Philip, S. Thomas, and V. Marin, “A highly compact epitope-based marker-suicide gene for more convenient and safer T-cell adoptive immunotherapy,” Blood, vol. 116, abstract 1473, pp. 629–630, 2010. View at Google Scholar
  133. F. Perosa, E. Favoino, C. Vicenti, F. Merchionne, and F. Dammacco, “Identification of an antigenic and immunogenic motif expressed by two 7-Mer rituximab-specific cyclic peptide mimotopes: implication for peptide-based active immunotherapy,” Journal of Immunology, vol. 179, no. 11, pp. 7967–7974, 2007. View at Google Scholar · View at Scopus
  134. G. Suntharalingam, M. R. Perry, S. Ward et al., “Cytokine storm in a phase 1 trial of the anti-CD28 monoclonal antibody TGN1412,” New England Journal of Medicine, vol. 355, no. 10, pp. 1018–1028, 2006. View at Publisher · View at Google Scholar · View at Scopus
  135. M. Chmielewski, O. Hahn, G. Rappl et al., “T cells that target carcinoembryonic antigen eradicate orthotopic pancreatic carcinomas without inducing autoimmune colitis in mice,” Gastroenterology, vol. 143, no. 4, pp. 1095–1107, 2012. View at Publisher · View at Google Scholar
  136. S. Kong, S. Sengupta, B. Tyler et al., “Suppression of human glioma xenografts with second-generation IL13R-specific chimeric antigen receptor-modified T cells,” Clinical Cancer Research, vol. 18, no. 21, pp. 5949–5960, 2012. View at Publisher · View at Google Scholar
  137. E. B. Santos, R. Yeh, J. Lee et al., “Sensitive in vivo imaging of T cells using a membrane-bound Gaussia princeps luciferase,” Nature Medicine, vol. 15, no. 3, pp. 338–344, 2009. View at Publisher · View at Google Scholar · View at Scopus
  138. G. Koehne, M. Doubrovin, E. Doubrovina et al., “Serial in vivo imaging of the targeted migration of human HSV-TK-transduced antigen-specific lymphocytes,” Nature Biotechnology, vol. 21, no. 4, pp. 405–413, 2003. View at Publisher · View at Google Scholar · View at Scopus
  139. S. S. Yaghoubi, M. C. Jensen, N. Satyamurthy et al., “Noninvasive detection of therapeutic cytolytic T cells with 18 F-FHBG PET in a patient with glioma,” Nature Reviews Clinical Oncology, vol. 6, no. 1, pp. 53–58, 2009. View at Google Scholar · View at Scopus
  140. M. M. Doubrovin, E. S. Doubrovina, P. Zanzonico, M. Sadelain, S. M. Larson, and R. J. O'Reilly, “In vivo imaging and quantitation of adoptively transferred human antigen-specific T cells transduced to express a human norepinephrine transporter gene,” Cancer Research, vol. 67, no. 24, pp. 11959–11969, 2007. View at Publisher · View at Google Scholar · View at Scopus
  141. E. Sharif-Paghaleh, K. Sunassee, R. Tavaré et al., “In vivo SPECT reporter gene imaging of regulatory T cells,” PLoS ONE, vol. 6, no. 10, Article ID e25857, 2011. View at Publisher · View at Google Scholar
  142. R. S. Warren, E. K. Bergsland, R. Pennathur-Das, J. Nemunaitis, A. P. Venook, and K. M. Hege, “Clinical studies of regional and systemic gene therapy with autologous CC49-z modified T cells in colorectal cancer metastatic to the liver,” Cancer Gene Therapy, vol. 5, pp. S1–S2, 1998. View at Google Scholar
  143. Q. Ma, R. M. Gonzalo-Daganzo, and R. P. Junghans, “Genetically engineered T cells as adoptive immunotherapy of cancer,” Cancer Chemotherapy and Biological Response Modifiers, vol. 20, pp. 315–341, 2002. View at Google Scholar · View at Scopus
  144. C. H. Lamers, S. Sleijfer, A. G. Vulto et al., “Treatment of metastatic renal cell carcinoma with autologous T-lymphocytes genetically retargeted against carbonic anhydrase IX: first clinical experience,” Journal of Clinical Oncology, vol. 24, no. 13, pp. e20–22, 2006. View at Publisher · View at Google Scholar · View at Scopus
  145. J. R. Park, D. L. DiGiusto, M. Slovak et al., “Adoptive transfer of chimeric antigen receptor re-directed cytolytic T lymphocyte clones in patients with neuroblastoma,” Molecular Therapy, vol. 15, no. 4, pp. 825–833, 2007. View at Publisher · View at Google Scholar · View at Scopus
  146. C. U. Louis, B. Savoldo, G. Dotti et al., “Antitumor activity and long-term fate of chimeric antigen receptor-positive T cells in patients with neuroblastoma,” Blood, vol. 118, no. 23, pp. 6050–6056, 2011. View at Publisher · View at Google Scholar
  147. M. C. Jensen, L. Popplewell, L. J. Cooper et al., “Antitransgene rejection responses contribute to attenuated persistence of adoptively transferred CD20/CD19-specific chimeric antigen receptor redirected T cells in humans,” Biology of Blood and Marrow Transplantation, vol. 16, no. 9, pp. 1245–1256, 2010. View at Publisher · View at Google Scholar · View at Scopus
  148. J. N. Kochenderfer, M. E. Dudley, S. A. Feldman et al., “B-cell depletion and remissions of malignancy along with cytokine-associated toxicity in a clinical trial of anti-CD19 chimeric-antigen-receptor-transduced T cells,” Blood, vol. 119, no. 12, pp. 2709–2720, 2012. View at Publisher · View at Google Scholar
  149. B. G. Till, M. C. Jensen, J. Wang et al., “CD20-specific adoptive immunotherapy for lymphoma using a chimeric antigen receptor with both CD28 and 4-1BB domains: pilot clinical trial results,” Blood, vol. 119, no. 17, pp. 3940–3950, 2012. View at Publisher · View at Google Scholar
  150. H. E. Heslop, “Safer cars,” Molecular Therapy, vol. 18, no. 4, pp. 661–662, 2010. View at Publisher · View at Google Scholar · View at Scopus
  151. R. J. Brentjens, J. B. Latouche, E. Santos et al., “Eradication of systemic B-cell tumors by genetically targeted human T lymphocytes co-stimulated by CD80 and interleukin-15,” Nature Medicine, vol. 9, no. 3, pp. 279–286, 2003. View at Publisher · View at Google Scholar · View at Scopus
  152. J. N. Kochenderfer, S. A. Feldman, Y. Zhao et al., “Construction and preclinical evaluation of an anti-CD19 chimeric antigen receptor,” Journal of Immunotherapy, vol. 32, no. 7, pp. 689–702, 2009. View at Publisher · View at Google Scholar · View at Scopus
  153. L. J. N. Cooper, M. S. Topp, L. M. Serrano et al., “T-cell clones can be rendered specific for CD19: toward the selective augmentation of the graft-versus-B-lineage leukemia effect,” Blood, vol. 101, no. 4, pp. 1637–1644, 2003. View at Publisher · View at Google Scholar · View at Scopus
  154. J. Wang, O. W. Press, C. G. Lindgren et al., “Cellular immunotherapy for follicular lymphoma using genetically modified CD20-specific CD8+ cytotoxic T lymphocytes,” Molecular Therapy, vol. 9, no. 4, pp. 577–586, 2004. View at Publisher · View at Google Scholar · View at Scopus
  155. J. Vera, B. Savoldo, S. Vigouroux et al., “T lymphocytes redirected against the κ light chain of human immunoglobulin efficiently kill mature B lymphocyte-derived malignant cells,” Blood, vol. 108, no. 12, pp. 3890–3897, 2006. View at Publisher · View at Google Scholar · View at Scopus
  156. B. Savoldo, C. M. Rooney, A. Di Stasi et al., “Epstein Barr virus-specific cytotoxic T lymphocytes expressing the anti-CD30ζ artificial chimeric T-cell receptor for immunotherapy of Hodgkin disease,” Blood, vol. 110, no. 7, pp. 2620–2630, 2007. View at Publisher · View at Google Scholar · View at Scopus
  157. V. Marin, I. Pizzitola, V. Agostoni et al., “Cytokine-induced killer cells for cell therapy of acute myeloid leukemia: improvement of their immune activity by expression of CD33-specific chimeric receptors,” Haematologica, vol. 95, no. 12, pp. 2144–2152, 2010. View at Publisher · View at Google Scholar · View at Scopus
  158. R. Thokala, H. Singh, S. Olivares, R. Champlin, and L. J. N. Cooper, “Targeting leukemias by CD123 specific chimeric antigen receptor,” Blood, vol. 118, abstract 1908, 2011. View at Google Scholar
  159. K. Mihara, K. Yanagihara, M. Takigahira et al., “Synergistic and persistent effect of T-cell immunotherapy with anti-CD19 or anti-CD38 chimeric receptor in conjunction with rituximab on B-cell non-Hodgkin lymphoma,” British Journal of Haematology, vol. 151, no. 1, pp. 37–46, 2010. View at Publisher · View at Google Scholar · View at Scopus
  160. K. Mihara, K. Yanagihara, M. Takigahira et al., “Activated T-cell-mediated immunotherapy with a chimeric receptor against CD38 in b-cell non-hodgkin lymphoma,” Journal of Immunotherapy, vol. 32, no. 7, pp. 737–743, 2009. View at Publisher · View at Google Scholar · View at Scopus
  161. M. Hudecek, T. M. Schmitt, S. Baskar et al., “The B-cell tumor-associated antigen ROR1 can be targeted with T cells modified to express a ROR1-specific chimeric antigen receptor,” Blood, vol. 116, no. 22, pp. 4532–4541, 2010. View at Publisher · View at Google Scholar · View at Scopus
  162. D. Moritz, W. Wels, J. Mattern, and B. Groner, “Cytotoxic T lymphocytes with a grafted recognition specificity for ERBB2- expressing tumor cells,” Proceedings of the National Academy of Sciences of the United States of America, vol. 91, no. 10, pp. 4318–4322, 1994. View at Google Scholar · View at Scopus
  163. U. Altenschmidt, E. Klundt, and B. Groner, “Adoptive transfer of in vitro-targeted, activated T lymphocytes results in total tumor regression,” Journal of Immunology, vol. 159, no. 11, pp. 5509–5515, 1997. View at Google Scholar · View at Scopus
  164. N. M. Haynes, M. J. Smyth, M. H. Kershaw, J. A. Trapani, and P. K. Darcy, “Fas-ligand-mediated lysis of erbB-2-expressing tumour cells by redirected cytotoxic T lymphocytes,” Cancer Immunology Immunotherapy, vol. 47, no. 5, pp. 278–286, 1999. View at Publisher · View at Google Scholar · View at Scopus
  165. J. H. Pinthus, T. Waks, K. Kaufman-Francis et al., “Immuno-gene therapy of established prostate tumors using chimeric receptor-redirected human lymphocytes,” Cancer Research, vol. 63, no. 10, pp. 2470–2476, 2003. View at Google Scholar · View at Scopus
  166. F. Turatti, M. Figini, P. Alberti, R. A. Willemsen, S. Canevari, and D. Mezzanzanica, “Highly efficient redirected anti-tumor activity of human lymphocytes transduced with a completely human chimeric immune receptor,” Journal of Gene Medicine, vol. 7, no. 2, pp. 158–170, 2005. View at Publisher · View at Google Scholar · View at Scopus
  167. N. Ahmed, M. Ratnayake, B. Savoldo et al., “Regression of experimental medulloblastoma following transfer of HER2-specific T cells,” Cancer Research, vol. 67, no. 12, pp. 5957–5964, 2007. View at Publisher · View at Google Scholar · View at Scopus
  168. S. Li, J. Yang, F. A. Urban et al., “Genetically engineered T cells expressing a HER2-specific chimeric receptor mediate antigen-specific tumor regression,” Cancer Gene Therapy, vol. 15, no. 6, pp. 382–392, 2008. View at Publisher · View at Google Scholar · View at Scopus
  169. H. Wang, H. Wei, R. Zhang et al., “Genetically targeted T cells eradicate established breast cancer in syngeneic mice,” Clinical Cancer Research, vol. 15, no. 3, pp. 943–950, 2009. View at Publisher · View at Google Scholar · View at Scopus
  170. N. Ahmed, V. S. Salsman, E. Yvon et al., “Immunotherapy for osteosarcoma: genetic modification of T cells overcomes low levels of tumor antigen expression,” Molecular Therapy, vol. 17, no. 10, pp. 1779–1787, 2009. View at Publisher · View at Google Scholar · View at Scopus
  171. Y. Zhao, Q. J. Wang, S. Yang et al., “A herceptin-based chimeric antigen receptor with modified signaling domains leads to enhanced survival of transduced T lymphocytes and antitumor activity,” Journal of Immunology, vol. 183, no. 9, pp. 5563–5574, 2009. View at Publisher · View at Google Scholar · View at Scopus
  172. N. Ahmed, V. S. Salsman, Y. Kew et al., “HER2-specific T cells target primary glioblastoma stem cells and induce regression of autologous experimental tumors,” Clinical Cancer Research, vol. 16, no. 2, pp. 474–485, 2010. View at Publisher · View at Google Scholar · View at Scopus
  173. N. Rainusso, V. S. Brawley, A. Ghazi et al., “Immunotherapy targeting HER2 with genetically modified T cells eliminates tumor-initiating cells in osteosarcoma,” Cancer Gene Therapy, vol. 19, no. 3, pp. 212–217, 2012. View at Publisher · View at Google Scholar
  174. R. A. Morgan, L. A. Johnson, and J. Davis, “Recognition of glioma stem cells by genetically modified T cells targeting EGFRvIII and development of adoptive cell therapy for glioma,” Human Gene Therapy, vol. 23, no. 10, pp. 1043–1053, 2012. View at Google Scholar
  175. P. K. Darcy, N. M. Haynes, M. B. Snook et al., “Redirected perforin-dependent lysis of colon carcinoma by ex vivo genetically engineered CTL,” Journal of Immunology, vol. 164, no. 7, pp. 3705–3712, 2000. View at Google Scholar · View at Scopus
  176. L. Ren-Heidenreich, G. T. Hayman, and K. T. Trevor, “Specific targeting of EGP-2+ tumor cells by primary lymphocytes modified with chimeric T cell receptors,” Human Gene Therapy, vol. 11, no. 1, pp. 9–19, 2000. View at Publisher · View at Google Scholar · View at Scopus
  177. T. Daly, R. E. Royal, M. H. Kershaw et al., “Recognition of human colon cancer by T cells transduced with a chimeric receptor gene,” Cancer Gene Therapy, vol. 7, no. 2, pp. 284–291, 2000. View at Google Scholar · View at Scopus
  178. E. Lanitis, M. Poussin, I. S. Hagemann et al., “Redirected antitumor activity of primary human lymphocytes transduced with a fully human anti-mesothelin chimeric receptor,” Molecular Therapy, vol. 20, no. 3, pp. 633–643, 2012. View at Publisher · View at Google Scholar
  179. A. Hombach, C. Heuser, R. Sircar et al., “T cell targeting of TAG72+ tumor cells by a chimeric receptor with antibody-like specificity for a carbohydrate epitope,” Gastroenterology, vol. 113, no. 4, pp. 1163–1170, 1997. View at Publisher · View at Google Scholar · View at Scopus
  180. M. C. Gong, J. B. Latouche, A. Krause, W. D. W. Heston, N. H. Bander, and M. Sadelain, “Cancer patient T cells genetically targeted to prostate-specific membrane antigen specifically lyse prostate cancer cells and release cytokines in response to prostate-specific membrane antigen,” Neoplasia, vol. 1, no. 2, pp. 123–127, 1999. View at Google Scholar · View at Scopus
  181. T. Zhang, B. A. Lemoi, and C. L. Sentman, “Chimeric NK-receptor-bearing T cells mediate antitumor immunotherapy,” Blood, vol. 106, no. 5, pp. 1544–1551, 2005. View at Publisher · View at Google Scholar · View at Scopus
  182. K. S. Kahlon, C. Brown, L. J. N. Cooper, A. Raubitschek, S. J. Forman, and M. C. Jensen, “Specific recognition and killing of glioblastoma multiforme by interleukin 13-zetakine redirected cytolytic T cells,” Cancer Research, vol. 64, no. 24, pp. 9160–9166, 2004. View at Publisher · View at Google Scholar · View at Scopus
  183. C. E. Brown, R. Starr, B. Aguilar et al., “Stem-like tumor-initiating cells isolated from IL13Rα2 expressing gliomas are targeted and killed by IL13-zetakine-redirected T cells,” Clinical Cancer Research, vol. 18, no. 8, pp. 2199–2209, 2012. View at Publisher · View at Google Scholar
  184. A. A. Chekmasova, T. D. Rao, Y. Nikhamin et al., “Successful eradication of established peritoneal ovarian tumors in SCID-Beige mice following adoptive transfer of T cells genetically targeted to the MUC16 antigen,” Clinical Cancer Research, vol. 16, no. 14, pp. 3594–3606, 2010. View at Publisher · View at Google Scholar · View at Scopus
  185. M. E. M. Weijtens, R. A. Willemsen, D. Valerio, K. Stam, and R. L. H. Bolhuis, “Single chain Ig/γ gene-redirected human T lymphocytes produce cytokines, specifically lyse tumor cells, and recycle lytic capacity,” Journal of Immunology, vol. 157, no. 2, pp. 836–843, 1996. View at Google Scholar · View at Scopus
  186. C. Rossig, C. M. Bollard, J. G. Nuchtern, D. A. Merchant, and M. K. Brenner, “Targeting of GD2-positive tumor cells by human T lymphocytes engineered to express chimeric T-cell receptor genes,” International Journal of Cancer, vol. 94, no. 2, pp. 228–236, 2001. View at Publisher · View at Google Scholar · View at Scopus
  187. S. Kailayangiri, B. Altvater, J. Meltzer et al., “The ganglioside antigen G D2 is surface-expressed in Ewing sarcoma and allows for MHC-independent immune targeting,” British Journal of Cancer, vol. 106, no. 6, pp. 1123–1133, 2012. View at Publisher · View at Google Scholar
  188. C. O. Yun, K. F. Nolan, E. J. Beecham, R. A. Reisfeld, and R. P. Junghans, “Targeting of T lymphocytes to melanoma cells through chimeric anti-GD3 immunoglobulin t-cell receptors,” Neoplasia, vol. 2, no. 5, pp. 449–459, 2000. View at Google Scholar · View at Scopus
  189. H. Abken, A. Hombach, C. Heuser, and U. Reinhold, “A novel strategy in the elimination of disseminated melanoma cells: chimeric receptors endow T cells with tumor specificity,” Recent Results in Cancer Research, vol. 158, pp. 249–264, 2001. View at Google Scholar · View at Scopus
  190. J. A. Westwood, M. J. Smyth, M. W. L. Teng et al., “Adoptive transfer of T cells modified with a humanized chimeric receptor gene inhibits growth of Lewis-Y-expressing tumors in mice,” Proceedings of the National Academy of Sciences of the United States of America, vol. 102, no. 52, pp. 19051–19056, 2005. View at Publisher · View at Google Scholar · View at Scopus
  191. P. C. Schuberth, G. Jakka, S. M. Jensen et al., “Effector memory and central memory NY-ESO-1-specific re-directed T cells for treatment of multiple myeloma,” Gene Therapy. In press.
  192. A. Morgenroth, M. Cartellieri, M. Schmitz et al., “Targeting of tumor cells expressing the prostate stem cell antigen (PSCA) using genetically engineered T-cells,” Prostate, vol. 67, no. 10, pp. 1121–1131, 2007. View at Publisher · View at Google Scholar · View at Scopus
  193. P. Hwu, J. C. Yang, R. Cowherd et al., “In vivo antitumor activity of T cells redirected with chimeric antibody/T-cell receptor genes,” Cancer Research, vol. 55, no. 15, pp. 3369–3373, 1995. View at Google Scholar · View at Scopus
  194. M. H. Kershaw, J. A. Westwood, and P. Hwu, “Dual-specific T cells combine proliferation and antitumor activity,” Nature Biotechnology, vol. 20, no. 12, pp. 1221–1227, 2002. View at Publisher · View at Google Scholar · View at Scopus
  195. A. Hekele, P. Dall, D. Moritz et al., “Growth retardation of tumors by adoptive transfer of cytotoxic T lymphocytes reprogrammed by CD44V6-specific SCFV:ζ-chimera,” International Journal of Cancer, vol. 68, no. 2, pp. 232–238, 1996. View at Publisher · View at Google Scholar
  196. P. Dall, I. Herrmann, B. Durst et al., “In vivo cervical cancer growth inhibition by genetically engineered cytotoxic T cells,” Cancer Immunology, Immunotherapy, vol. 54, no. 1, pp. 51–60, 2005. View at Publisher · View at Google Scholar · View at Scopus
  197. N. K. V. Cheung, H. F. Guo, S. Modak, and I. Y. Cheung, “Anti-idiotypic antibody facilitates scFv chimeric immune receptor gene transduction and clonal expansion of human lymphocytes for tumor therapy,” Hybridoma and Hybridomics, vol. 22, no. 4, pp. 209–218, 2003. View at Google Scholar · View at Scopus
  198. D. E. Gilham, A. O'Neil, C. Hughes et al., “Primary polyclonal human T lymphocytes targeted to carcino-embryonic antigens and neural cell adhesion molecule tumor antigens by CD3ζ-based chimeric immune receptors,” Journal of Immunotherapy, vol. 25, no. 2, pp. 139–151, 2002. View at Publisher · View at Google Scholar · View at Scopus
  199. T. M. J. Niederman, Z. Ghogawala, B. S. Carter, H. S. Tompkins, M. M. Russell, and R. C. Mulligan, “Antitumor activity of cytotoxic T lymphocytes engineered to target vascular endothelial growth factor receptors,” Proceedings of the National Academy of Sciences of the United States of America, vol. 99, no. 10, pp. 7009–7014, 2002. View at Publisher · View at Google Scholar · View at Scopus
  200. M. H. Kershaw, J. A. Westwood, Z. Zhu, L. Witte, S. K. Libutti, and P. Hwu, “Generation of gene-modified T cells reactive against the angiogenic kinase insert domain-containing receptor (KDR) found on tumor vasculature,” Human Gene Therapy, vol. 11, no. 18, pp. 2445–2452, 2000. View at Publisher · View at Google Scholar · View at Scopus
  201. H. R. Jiang, D. E. Gilham, K. Mulryan, N. Kirillova, R. E. Hawidns, and P. L. Stern, “Combination of vaccination and chimeric receptor expressing T cells provides improved active therapy of tumors,” Journal of Immunology, vol. 177, no. 7, pp. 4288–4298, 2006. View at Google Scholar · View at Scopus
  202. S. Gattenlöhner, A. Marx, B. Markfort et al., “Rhabdomyosarcoma lysis by T cells expressing a human autoantibody-based chimeric receptor targeting the fetal acetylcholine receptor,” Cancer Research, vol. 66, no. 1, pp. 24–28, 2006. View at Publisher · View at Google Scholar · View at Scopus
  203. M. Casucci, L. Falcone, and B. Nicolis di Robilant, “Dual transgenesis of T cells with a CD44v6 CAR and a suicide gene for the safe eradication of myeloid leukemia and myeloma,” Molecular Therapy, vol. 20, no. S1, abstract 465, p. S180, 2012. View at Google Scholar
  204. S. D. Patel, M. Moskalenko, T. Tian et al., “T-cell killing of heterogenous tumor or viral targets with bispecific chimeric immune receptors,” Cancer Gene Therapy, vol. 7, no. 8, pp. 1127–1134, 2000. View at Google Scholar · View at Scopus
  205. C. Uherek, T. Tonn, B. Uherek et al., “Retargeting of natural killer-cell cytolytic activity to ErbB2-expressing cancer cells results in efficient and selective tumor cell destruction,” Blood, vol. 100, no. 4, pp. 1265–1273, 2002. View at Google Scholar · View at Scopus
  206. H. E. Daldrup-Link, R. Meier, M. Rudelius et al., “In vivo tracking of genetically engineered, anti-HER2/neu directed natural killer cells to HER2/neu positive mammary tumors with magnetic resonance imaging,” European Radiology, vol. 15, no. 1, pp. 4–13, 2005. View at Publisher · View at Google Scholar · View at Scopus
  207. R. Meier, M. Piert, G. Piontek et al., “Tracking of [18F]FDG-labeled natural killer cells to HER2/neu-positive tumors,” Nuclear Medicine and Biology, vol. 35, no. 5, pp. 579–588, 2008. View at Publisher · View at Google Scholar · View at Scopus
  208. H. J. Pegram, J. T. Jackson, M. J. Smyth, M. H. Kershaw, and P. K. Darcy, “Adoptive transfer of gene-modified primary NK cells can specifically inhibit tumor progression in vivo,” Journal of Immunology, vol. 181, no. 5, pp. 3449–3455, 2008. View at Google Scholar · View at Scopus
  209. A. Kruschinski, A. Moosmann, I. Poschke et al., “Engineering antigen-specific primary human NK cells against HER-2 positive carcinomas,” Proceedings of the National Academy of Sciences of the United States of America, vol. 105, no. 45, pp. 17481–17486, 2008. View at Publisher · View at Google Scholar · View at Scopus
  210. A. Biglari, T. D. Southgate, L. J. Fairbairn, and D. E. Gilham, “Human monocytes expressing a CEA-specific chimeric CD64 receptor specifically target CEA-expressing tumour cells in vitro and in vivo,” Gene Therapy, vol. 13, no. 7, pp. 602–610, 2006. View at Publisher · View at Google Scholar · View at Scopus
  211. S. Tammana, X. Huang, M. Wong et al., “4-1BB and CD28 signaling plays a synergistic role in redirecting umbilical cord blood t cells against b-cell malignancies,” Human Gene Therapy, vol. 21, no. 1, pp. 75–86, 2010. View at Publisher · View at Google Scholar · View at Scopus
  212. M. R. Roberts, K. S. Cooke, A. C. Tran et al., “Antigen-specific cytolysis by neutrophils and NK cells expressing chimeric immune receptors bearing or signaling domains,” Journal of Immunology, vol. 161, no. 1, pp. 375–384, 1998. View at Google Scholar · View at Scopus
  213. G. Wang, R. K. Chopra, R. E. Royal, J. C. Yang, S. A. Rosenberg, and P. Hwu, “A T cell-independent antitumor response in mice with bone marrow cells retrovirally transduced with an antibody/Fc-γ chain chimetic receptor gene recognizing a human ovarian cancer antigen,” Nature Medicine, vol. 4, no. 2, pp. 168–172, 1998. View at Publisher · View at Google Scholar · View at Scopus
  214. Y. Xu, P. K. Darcy, and M. H. Kershaw, “Tumor-specific dendritic cells generated by genetic redirection of Toll-like receptor signaling against the tumor-associated antigen, erbB2,” Cancer Gene Therapy, vol. 14, no. 9, pp. 773–780, 2007. View at Publisher · View at Google Scholar · View at Scopus
  215. C. Cruz, K. Micklethwaite, B. Savoldo et al., “Infusion of CD19-directed/multivirus-specific CTLs post HSCT for B cell malignancies,” Molecular Therapy, vol. 20, no. S1, abstract 536, p. S207, 2012. View at Google Scholar
  216. S. F. Slovin, X. Wang, and O. Borquez-Ojeda, “Targeting Castration Resistant Prostate Cancer (CRPC) with autologous PSMA-directed chimeric antigen receptor T cells,” Molecular Therapy, vol. 20, no. S1, abstract 81, p. S33, 2012. View at Google Scholar
  217. R. P. Junghans, R. Rathore, and Q. Ma, “Phase 1 trial of anti-PSMA designed T cells in advanced prostate cancer,” Journal of Clinical Oncology, vol. 29, no. S7, abstract 130, 2011. View at Google Scholar
  218. L. E. Kandalaft, D. J. Powell, and G. Coukos, “A phase I clinical trial of adoptive transfer of folate receptor-alpha redirected autologous T cells for recurrent ovarian cancer,” Journal of Translational Medicine, vol. 10, no. 1, article 157, 2012. View at Publisher · View at Google Scholar