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Clinical and Developmental Immunology
Volume 2012 (2012), Article ID 831090, 7 pages
http://dx.doi.org/10.1155/2012/831090
Review Article

Impact of Temozolomide on Immune Response during Malignant Glioma Chemotherapy

1Brain Tumor Laboratory, Roger Williams Medical Center, 825 Chalkstone Avenue, Prior 222, Providence, RI 02908, USA
2Department of Neurological Surgery, Boston University School of Medicine, Boston, MA 02118, USA

Received 11 July 2012; Revised 10 September 2012; Accepted 20 September 2012

Academic Editor: Steven Eric Finkelstein

Copyright © 2012 Sadhak Sengupta et al. 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. “Central Brain Tumor Registry of the United States (CTBRUS) Report 2010,” http://www.cbtrus.org/factsheet/factsheet.html.
  2. R. Stupp, W. P. Mason, M. J. Van Den Bent et al., “Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma,” The New England Journal of Medicine, vol. 352, no. 10, pp. 987–996, 2005. View at Publisher · View at Google Scholar · View at Scopus
  3. L. M. DeAngelis, “Brain tumors,” The New England Journal of Medicine, vol. 344, no. 2, pp. 114–123, 2001. View at Publisher · View at Google Scholar · View at Scopus
  4. E. R. Laws, I. F. Parney, W. Huang et al., “Survival following surgery and prognostic factors for recently diagnosed malignant glioma: data from the glioma outcomes project,” Journal of Neurosurgery, vol. 99, no. 3, pp. 467–473, 2003. View at Scopus
  5. D. A. Wainwright, P. Nigam, B. Thaci, et al., “Recent developments on immunotherapy for brain cancer,” Expert Opinions in Emerging Drugs, vol. 17, no. 2, pp. 181–202, 2012. View at Publisher · View at Google Scholar
  6. C. E. Rolle, S. Sengupta, and M. S. Lesniak, “Mechanisms of immune evasion by gliomas,” Advances in Experimental Medicine and Biology, vol. 746, pp. 53–76, 2012. View at Publisher · View at Google Scholar
  7. D. A. Wainwright, S. Sengupta, Y. Han, I. V. Ulasov, and M. S. Lesniak, “The presence of IL-17A and T helper 17 cells in experimental mouse brain tumors and human gliom,” PLoS ONE, vol. 5, no. 10, Article ID e15390, 2010. View at Publisher · View at Google Scholar · View at Scopus
  8. S. Sengupta, S. Nandi, E. S. Hindi, D. A. Wainwright, Y. Han, and M. S. Lesniak, “Short hairpin RNA-mediated fibronectin knockdown delays tumor growth in a mouse glioma model,” Neoplasia, vol. 12, no. 10, pp. 837–847, 2010. View at Publisher · View at Google Scholar · View at Scopus
  9. V. Donato, A. Papaleo, A. Castrichino et al., “Prognostic implication of clinical and pathologic features in patients with glioblastoma multiforme treated with concomitant radiation plus temozolomide,” Tumori, vol. 93, no. 3, pp. 248–256, 2007. View at Scopus
  10. R. Jalali, A. Basu, T. Gupta et al., “Encouraging experience of concomitant Temozolomide with radiotherapy followed by adjuvant Temozolomide in newly diagnosed glioblastoma multiforme: single institution experience,” British Journal of Neurosurgery, vol. 21, no. 6, pp. 583–587, 2007. View at Publisher · View at Google Scholar · View at Scopus
  11. C. E. Rolle, S. Sengupta, and M. S. Lesniak, “Challenges in clinical design of immunotherapy trials for malignant glioma,” Neurosurgery Clinics of North America, vol. 21, no. 1, pp. 201–214, 2010. View at Publisher · View at Google Scholar · View at Scopus
  12. R. Stupp, M. E. Hegi, W. P. Mason, et al., “Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial,” The Lancet Oncology, vol. 10, no. 5, pp. 459–466, 2009. View at Publisher · View at Google Scholar
  13. American Cancer Society, Brain and Spinal Cord Tumors in Children, Atlanta, Ga, USA, 2010.
  14. FDA Approval for Temozolomide, National Cancer Institute, 2010, http://www.cancer.gov/cancertopics/druginfo/fda-temozolomide.
  15. M. M. Mrugala, M. C. Chamberlain, and F. Hutchinson, “Mechanisms of disease: temozolomide and glioblastoma—look to the future,” Nature Clinical Practice Oncology, vol. 5, no. 8, pp. 476–486, 2008. View at Publisher · View at Google Scholar · View at Scopus
  16. R. O. Mirimanoff, T. Gorlia, W. Mason et al., “Radiotherapy and temozolomide for newly diagnosed glioblastoma: recursive partitioning analysis of the EORTC 26981/22981-NCIC CE3 phase III randomized trial,” Journal of Clinical Oncology, vol. 24, no. 16, pp. 2563–2569, 2006. View at Publisher · View at Google Scholar · View at Scopus
  17. L. S. Ashby and T. C. Ryken, “Management of malignant glioma: steady progress with multimodal approaches,” Neurosurgical Focus, vol. 20, no. 4, p. E3, 2006. View at Publisher · View at Google Scholar · View at Scopus
  18. A. F. Carpentier and Y. Meng, “Recent advances in immunotherapy for human glioma,” Current Opinion in Oncology, vol. 18, no. 6, pp. 631–636, 2006. View at Publisher · View at Google Scholar · View at Scopus
  19. V. A. Trinh, S. P. Patel, and W. J. Hwu, “The safety of temozolomide in the treatment of malignancies,” Expert Opinion on Drug Safety, vol. 8, no. 4, pp. 493–499, 2009. View at Publisher · View at Google Scholar · View at Scopus
  20. J. H. Sampson, K. D. Aldape, G. E. Archer et al., “Greater chemotherapy-induced lymphopenia enhances tumor-specific immune responses that eliminate EGFRvIII-expressing tumor cells in patients with glioblastoma,” Neuro-Oncology, vol. 13, no. 3, pp. 324–333, 2011. View at Publisher · View at Google Scholar · View at Scopus
  21. G. C. De Gast, D. Batchelor, M. J. Kersten et al., “Temozolomide followed by combined immunotherapy with GM-CSF, low-dose IL2 and IFNα in patients with metastatic melanoma,” British Journal of Cancer, vol. 88, no. 2, pp. 175–180, 2003. View at Publisher · View at Google Scholar · View at Scopus
  22. B. J. Denny, R. T. Wheelhouse, M. F. G. Stevens, L. L. H. Tsang, and J. A. Slack, “NMR and molecular modeling investigation of the mechanism of activation of the antitumor drug temozolomide and its interaction with DNA,” Biochemistry, vol. 33, no. 31, pp. 9045–9051, 1994. View at Scopus
  23. S. Cai, Y. Xu, R. J. Cooper et al., “Mitochondrial targeting of human O6-methylguanine DNA methyltransferase protects against cell killing by chemotherapeutic alkylating agents,” Cancer Research, vol. 65, no. 8, pp. 3319–3327, 2005. View at Scopus
  24. R. N. Trivedi, K. H. Almeida, J. L. Fornsaglio, S. Schamus, and R. W. Sobol, “The role of base excision repair in the sensitivity and resistance to temozolomide-mediated cell death,” Cancer Research, vol. 65, no. 14, pp. 6394–6400, 2005. View at Publisher · View at Google Scholar · View at Scopus
  25. A. M. Donson, S. O. Addo-Yobo, M. H. Handler, L. Gore, and N. K. Foreman, “MGMT promoter methylation correlates with survival benefit and sensitivity to temozolomide in pediatric glioblastoma,” Pediatric Blood and Cancer, vol. 48, no. 4, pp. 403–407, 2007. View at Publisher · View at Google Scholar · View at Scopus
  26. W. P. Roos, L. F. Z. Batista, S. C. Naumann et al., “Apoptosis in malignant glioma cells triggered by the temozolomide-induced DNA lesion O6-methylguanine,” Oncogene, vol. 26, no. 2, pp. 186–197, 2007. View at Publisher · View at Google Scholar · View at Scopus
  27. M. E. Hegi, A. C. Diserens, T. Gorlia et al., “MGMT gene silencing and benefit from temozolomide in glioblastoma,” The New England Journal of Medicine, vol. 352, no. 10, pp. 997–1003, 2005. View at Publisher · View at Google Scholar · View at Scopus
  28. A. E. Pegg, M. E. Dolan, and R. C. Moschel, “Structure, function, and inhibition of O6-alkylguanine-DNA alkyltransferase,” Progress in Nucleic Acid Research and Molecular Biology, vol. 51, pp. 167–223, 1995. View at Scopus
  29. M. E. Dolan, “Inhibition of DNA repair as a means of increasing the antitumor activity of DNA reactive agents,” Advanced Drug Delivery Reviews, vol. 26, no. 2-3, pp. 105–118, 1997. View at Publisher · View at Google Scholar · View at Scopus
  30. K. A. Jaeckle, H. J. Eyre, J. J. Townsend et al., “Correlation of tumor O6 methylguanine-DNA methyltransferase levels with survival of malignant astrocytoma patients treated with bis- chloroethylnitrosourea: a Southwest Oncology Group study,” Journal of Clinical Oncology, vol. 16, no. 10, pp. 3310–3315, 1998. View at Scopus
  31. S. L. Gerson, “Clinical relevance of MGMT in the treatment of cancer,” Journal of Clinical Oncology, vol. 20, no. 9, pp. 2388–2399, 2002. View at Publisher · View at Google Scholar · View at Scopus
  32. C. Happold, P. Roth, W. Wick, et al., “Distinct molecular mechanisms of acquired resistance to temozolomide in glioblastoma cells,” Journal of Neurochemistry, 2012. In press. View at Publisher · View at Google Scholar
  33. Q. Pan, X. J. Yang, H. M. Wang, et al., “Chemoresistance to temozolomide in human glioma cell line U251 is associated with increased activity of O6-methylguanine-DNA methyltransferase and can be overcome by metronomic temozolomide regimen,” Cell Biochemistry and Biophysics, vol. 62, no. 1, pp. 185–191, 2012. View at Publisher · View at Google Scholar
  34. G. Jiang, Z. P. Wei, D. S. Pei, Y. Xin, Y. Q. Liu, and J. N. Zheng, “A novel approach to overcome temozolomide resistance in glioma and melanoma: inactivation of MGMT by gene therapy,” Biochemical and Biophysical Research Communications, vol. 406, no. 3, pp. 311–314, 2011. View at Publisher · View at Google Scholar · View at Scopus
  35. K. A. Van Nifterik, J. Van Den Berg, W. F. Van Der Meide et al., “Absence of the MGMT protein as well as methylation of the MGMT promoter predict the sensitivity for temozolomide,” British Journal of Cancer, vol. 103, no. 1, pp. 29–35, 2010. View at Publisher · View at Google Scholar · View at Scopus
  36. M. Nagane, K. Kobayashi, A. Ohnishi, S. Shimizu, and Y. Shiokawa, “Prognostic significance of O6-methylguanine-DNA methyltransferase protein expression in patients with recurrent glioblastoma treated with temozolomide,” Japanese Journal of Clinical Oncology, vol. 37, no. 12, pp. 897–906, 2007. View at Publisher · View at Google Scholar · View at Scopus
  37. M. Hermisson, A. Klumpp, W. Wick et al., “O6-methylguanine DNA methyltransferase and p53 status predict temozolomide sensitivity in human malignant glioma cells,” Journal of Neurochemistry, vol. 96, no. 3, pp. 766–776, 2006. View at Publisher · View at Google Scholar · View at Scopus
  38. G. J. Kitange, B. L. Carlson, M. A. Schroeder et al., “Induction of MGMT expression is associated with temozolomide resistance in glioblastoma xenografts,” Neuro-Oncology, vol. 11, no. 3, pp. 281–291, 2009. View at Publisher · View at Google Scholar · View at Scopus
  39. M. J. Riemenschneider, M. E. Hegi, and G. Reifenberger, “MGMT promoter methylation in malignant gliomas,” Targeted Oncology, vol. 5, no. 3, pp. 161–165, 2010. View at Publisher · View at Google Scholar · View at Scopus
  40. J. Zhang, M. F. G. Stevens, C. A. Laughton, S. Madhusudan, and T. D. Bradshaw, “Acquired resistance to temozolomide in glioma cell lines: molecular mechanisms and potential translational applications,” Oncology, vol. 78, no. 2, pp. 103–114, 2010. View at Publisher · View at Google Scholar · View at Scopus
  41. C. S. Brock, E. S. Newlands, S. R. Wedge et al., “Phase I trial of temozolomide using an extended continuous oral schedule,” Cancer Research, vol. 58, no. 19, pp. 4363–4367, 1998. View at Scopus
  42. E. Alvino, R. Pepponi, E. Pagani et al., “O6-Benzylguanine enhances the in vitro immunotoxic activity of temozolomide on natural or antigen-dependent immunity,” Journal of Pharmacology and Experimental Therapeutics, vol. 291, no. 3, pp. 1292–1300, 1999. View at Scopus
  43. R. B. Khan, J. J. Raizer, M. G. Malkin, K. A. Bazylewicz, and L. E. Abrey, “A phase II study of extended low-dose temozolomide in recurrent malignant gliomas,” Neuro-Oncology, vol. 4, no. 1, pp. 39–43, 2002. View at Publisher · View at Google Scholar · View at Scopus
  44. A. B. Heimberger, W. Sun, S. F. Hussain et al., “Immunological responses in a patient with glioblastoma multiforme treated with sequential courses of temozolomide and immunotherapy: case study,” Neuro-Oncology, vol. 10, no. 1, pp. 98–103, 2008. View at Publisher · View at Google Scholar · View at Scopus
  45. L. W. Vestermark, E. Holtved, R. Dahlrot, et al., “A phase II study of thalidomide and temozolomide in patients with brain metastases from malignant melanoma: lymphopenia correlates with response,” Ecancermedicalscience, vol. 2, article 91, 2008.
  46. R. Stupp, P. Y. Dietrich, S. O. Kraljevic et al., “Promising survival for patients with newly diagnosed glioblastoma multiforme treated with concomitant radiation plus temozolomide followed by adjuvant temozolomide,” Journal of Clinical Oncology, vol. 20, no. 5, pp. 1375–1382, 2002. View at Publisher · View at Google Scholar · View at Scopus
  47. M. Gander, S. Leyvraz, L. Decosterd et al., “Sequential administration of temozolomide and fotemustine: depletion of O6-alkyl guanine-DNA transferase in blood lymphocytes and in tumours,” Annals of Oncology, vol. 10, no. 7, pp. 831–838, 1999. View at Publisher · View at Google Scholar · View at Scopus
  48. M. Briegert and B. Kaina, “Human monocytes, but not dendritic cells derived from them, are defective in base excision repair and hypersensitive to methylating agents,” Cancer Research, vol. 67, no. 1, pp. 26–31, 2007. View at Publisher · View at Google Scholar · View at Scopus
  49. M. Briegert, A. H. Enk, and B. Kaina, “Change in expression of MGMT during maturation of human monocytes into dendritic cells,” DNA Repair, vol. 6, no. 9, pp. 1255–1263, 2007. View at Publisher · View at Google Scholar · View at Scopus
  50. X. Zhu, M. Fujita, L. A. Snyder, and H. Okada, “Systemic delivery of neutralizing antibody targeting CCL2 for glioma therapy,” Journal of Neuro-Oncology, vol. 104, no. 1, pp. 83–92, 2011. View at Publisher · View at Google Scholar · View at Scopus
  51. I. Desbaillets, M. Tada, N. De Tribolet, A. C. Diserens, M. F. Hamou, and E. G. Van Meir, “Human astrocytomas and glioblastomas express monocyte chemoattractant protein-1 (MCP-1) in vivo and in vitro,” International Journal of Cancer, vol. 58, no. 2, pp. 240–247, 1994. View at Publisher · View at Google Scholar · View at Scopus
  52. S. Y. Leung, M. P. Wong, L. P. Chung, A. S. Y. Chan, and S. T. Yuen, “Monocyte chemoattractant protein-1 expression and macrophage infiltration in gliomas,” Acta Neuropathologica, vol. 93, no. 5, pp. 518–527, 1997. View at Publisher · View at Google Scholar · View at Scopus
  53. B. Huang, Z. Lei, J. Zhao et al., “CCL2/CCR2 pathway mediates recruitment of myeloid suppressor cells to cancers,” Cancer Letters, vol. 252, no. 1, pp. 86–92, 2007. View at Publisher · View at Google Scholar · View at Scopus
  54. M. Bauer, M. Goldstein, D. Heylmann, et al., “Human monocytes undergo excessive apoptosis following temozolomide activating the ATM/ATR pathway while dendritic cells and macrophages are resistant,” PLoS ONE, vol. 7, no. 6, Article ID e39956, 2012.
  55. C. E. Fadul, J. L. Fisher, J. Gui, T. H. Hampton, A. L. Côté, and M. S. Ernstoff, “Immune modulation effects of concomitant temozolomide and radiation therapy on peripheral blood mononuclear cells in patients with glioblastoma multiforme,” Neuro-Oncology, vol. 13, no. 4, pp. 393–400, 2011. View at Publisher · View at Google Scholar · View at Scopus
  56. C. Banissi, F. Ghiringhelli, L. Chen, and A. F. Carpentier, “Treg depletion with a low-dose metronomic temozolomide regimen in a rat glioma model,” Cancer Immunology, Immunotherapy, vol. 58, no. 10, pp. 1627–1634, 2009. View at Publisher · View at Google Scholar · View at Scopus
  57. Y. B. Su, S. Sohn, S. E. Krown et al., “Selective CD4+ lymphopenia in melanoma patients treated with temozolomide: a toxicity with therapeutic implications,” Journal of Clinical Oncology, vol. 22, no. 4, pp. 610–616, 2004. View at Publisher · View at Google Scholar · View at Scopus
  58. D. A. Mitchell, X. Cui, R. J. Schmittling, et al., “Monoclonal antibody blockade of IL-2 receptor alpha during lymphopenia selectively depletes regulatory T cells in mice and humans,” Blood, vol. 118, no. 11, pp. 3003–3012, 2011. View at Publisher · View at Google Scholar
  59. J. H. Sampson, R. J. Schmittling, G. E. Archer, et al., “A pilot study of IL-2Ralpha blockade during lymphopenia depletes regulatory T-cells and correlates with enhanced immunity in patients with glioblastoma,” PLoS ONE, vol. 7, no. 2, Article ID e31046, 2012.
  60. R. J. North, “Cyclophosphamide-facilitated adoptive immunotherapy of an established tumor depends on elimination of tumor-induced suppressor T cells,” Journal of Experimental Medicine, vol. 155, no. 4, pp. 1063–1074, 1982. View at Scopus
  61. M. E. Dudley, J. R. Wunderlich, J. C. Yang et al., “Adoptive cell transfer therapy following non-myeloablative but lymphodepleting chemotherapy for the treatment of patients with refractory metastatic melanoma,” Journal of Clinical Oncology, vol. 23, no. 10, pp. 2346–2357, 2005. View at Publisher · View at Google Scholar · View at Scopus
  62. 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
  63. B. Neyns, A. Tosoni, W. J. Hwu, and D. A. Reardon, “Dose-dense temozolomide regimens: antitumor activity, toxicity, and immunomodulatory effects,” Cancer, vol. 116, no. 12, pp. 2868–2877, 2010. View at Publisher · View at Google Scholar · View at Scopus
  64. C. E. Fadul, J. L. Fisher, T. H. Hampton et al., “Immune response in patients with newly diagnosed glioblastoma multiforme treated with intranodal autologous tumor lysate-dendritic cell vaccination after radiation chemotherapy,” Journal of Immunotherapy, vol. 34, no. 4, pp. 382–389, 2011. View at Publisher · View at Google Scholar · View at Scopus
  65. T. G. Kim, C. H. Kim, J. S. Park et al., “Immunological factors relating to the antitumor effect of temozolomide chemoimmunotherapy in a murine glioma model,” Clinical and Vaccine Immunology, vol. 17, no. 1, pp. 143–153, 2010. View at Publisher · View at Google Scholar · View at Scopus
  66. E. Ishikawa, T. Yamamoto, N. Sakamoto et al., “Low peripheral lymphocyte count before focal radiotherapy plus concomitant temozolomide predicts severe lymphopenia during malignant glioma treatment,” Neurologia Medico-Chirurgica, vol. 50, no. 8, pp. 638–644, 2010. View at Publisher · View at Google Scholar · View at Scopus
  67. V. Ridola, G. Barone, I. Lazzareschi, A. Ruggiero, D. Rizzo, and R. Riccardi, “Feasibility study of 21-day-on/7-day-off temozolomide in children with brain tumors,” Journal of Neuro-Oncology, vol. 103, no. 1, pp. 147–153, 2011. View at Publisher · View at Google Scholar · View at Scopus
  68. J. N. Sarkaria, E. Galanis, W. Wu et al., “Combination of temsirolimus (CCI-779) with chemoradiation in newly diagnosed glioblastoma multiforme (GBM) (NCCTG trial N027D) is associated with increased infectious risks,” Clinical Cancer Research, vol. 16, no. 22, pp. 5573–5580, 2010. View at Publisher · View at Google Scholar · View at Scopus
  69. S. D'Atri, G. Graziani, P. M. Lacal et al., “Attenuation of O6-methylguanine-DNA methyltransferase activity and mRNA levels by cisplatin and temozolomide in Jurkat cells,” Journal of Pharmacology and Experimental Therapeutics, vol. 294, no. 2, pp. 664–671, 2000. View at Scopus
  70. N. Sawai, S. Zhou, E. F. Vanin, P. Houghton, T. P. Brent, and B. P. Sorrentino, “Protection and in vivo selection of hematopoietic stem cells using temozolomide, O6-benzylguanine, and an alkyltransferase-expressing retroviral vector,” Molecular Therapy, vol. 3, no. 1, pp. 78–87, 2001. View at Publisher · View at Google Scholar · View at Scopus
  71. M. Remington, J. Chtchetinin, K. Ancheta, P. L. Nghiemphu, T. Cloughesy, and A. Lai, “The L84F polymorphic variant of human O6-methylguanine-DNA methyltransferase alters stability in U87MG glioma cells but not temozolomide sensitivity,” Neuro-Oncology, vol. 11, no. 1, pp. 22–32, 2009. View at Publisher · View at Google Scholar · View at Scopus
  72. S. P. Zielske, J. S. Reese, K. T. Lingas, J. R. Donze, and S. L. Gerson, “In vivo selection of MGMT(P140K) lentivirus-transduced human NOD/SCID repopulating cells without pretransplant irradiation conditioning,” Journal of Clinical Investigation, vol. 112, no. 10, pp. 1561–1570, 2003. View at Publisher · View at Google Scholar · View at Scopus
  73. K. E. Pollok, J. R. Hartwell, A. Braber et al., “In vivo selection of human hematopoietic cells in a xenograft model using combined pharmacologic and genetic manipulations,” Human Gene Therapy, vol. 14, no. 18, pp. 1703–1714, 2003. View at Scopus
  74. T. Neff, B. C. Beard, L. J. Peterson, P. Anandakumar, J. Thompson, and H. P. Kiem, “Polyclonal chemoprotection against temozolomide in a large-animal model of drug resistance gene therapy,” Blood, vol. 105, no. 3, pp. 997–1002, 2005. View at Publisher · View at Google Scholar · View at Scopus
  75. S. Gerull, B. C. Beard, L. J. Peterson, T. Neff, and H. P. Kiem, “In vivo selection and chemoprotection after drug resistance gene therapy in a nonmyeloablative allogeneic transplantation setting in dogs,” Human Gene Therapy, vol. 18, no. 5, pp. 451–456, 2007. View at Publisher · View at Google Scholar · View at Scopus
  76. A. Dasgupta, D. McCarty, and H. T. Spencer, “Engineered drug-resistant immunocompetent cells enhance tumor cell killing during a chemotherapy challenge,” Biochemical and Biophysical Research Communications, vol. 391, no. 1, pp. 170–175, 2010. View at Publisher · View at Google Scholar · View at Scopus
  77. P. Maier, I. Spier, S. Laufs et al., “Chemoprotection of human hematopoietic stem cells by simultaneous lentiviral overexpression of multidrug resistance 1 and O6-methylguanine-DNA methyltransferase P140K,” Gene Therapy, vol. 17, no. 3, pp. 389–399, 2010. View at Publisher · View at Google Scholar · View at Scopus
  78. S. Kong, S. Sengupta, B. Tyler, et al., “Suppression of human glioma xenografts with 2nd generation IL13R-specific chimeric antigen receptor-modified T cells,” Clinical Cancer Research, 2012. In press. View at Publisher · View at Google Scholar
  79. M. J. Stastny, C. E. Brown, C. Ruel, and M. C. Jensen, “Medulloblastomas expressing IL13Rα2 are targets for IL13-zetakine+ cytolytic T cells,” Journal of Pediatric Hematology/Oncology, vol. 29, no. 10, pp. 669–677, 2007. View at Publisher · View at Google Scholar · View at Scopus
  80. 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
  81. 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
  82. S. S. Bullain, A. Sahin, O. Szentirmai et al., “Genetically engineered T cells to target EGFRvIII expressing glioblastoma,” Journal of Neuro-Oncology, vol. 94, no. 3, pp. 373–382, 2009. View at Publisher · View at Google Scholar · View at Scopus
  83. M. Ohno, A. Natsume, K. Ichiro Iwami et al., “Retrovirally engineered T-cell-based immunotherapy targeting type III variant epidermal growth factor receptor, a glioma-associated antigen,” Cancer Science, vol. 101, no. 12, pp. 2518–2524, 2010. View at Publisher · View at Google Scholar · View at Scopus
  84. M. C. Kizilarslanoglu, S. Aksoy, N. O. Yildirim, et al., “Temozolomide-related infections: review of the literature,” Journal of Balkan Union of Oncology, vol. 16, no. 3, pp. 547–550, 2011.