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Hapten treatment | Author, year | Hapten used for treatment, alone and in combination | Tumor type/cell line used in animal and human studies | Route of administration of haptens and hapten-modified products | Observations |
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Ex vivo haptenation | Hamaoka et al., 1979 [21] | TNBS, TNP-MGG sensitization and TNP-D-GL pretreatment | X5563 cells in C3H/HeN mice | i.p. TNP-X5563 injection | Significantly delayed tumor growth for up to 15 days |
Fujiwara et al., 1980 [22] | TNBS, TNP-MGG sensitization and TNP-D-GL pretreatment | LSTRA cells in Balb/c mice | i.p. TNP-X5563 injection | Significantly delayed tumor growth for up to 10 days |
Flood et al., 1987 [23] | TNBS, N/A | Progressor and regressor fibrosarcomas in C3H/HeN mice | s.c. TNP-regressor/TNP-progressor injection | Significantly delayed tumor growth for up to 30 days |
Berd et al., 1993 [30] | DNFB, DNFB sensitization and CY pretreatment combined with BCG and nodal resection | Stages III and IV metastatic melanoma in patients | i.d. DNP-autologous melanoma injection | 5/46 patient responses for metastatic melanoma and 59% 2-year survival postnodal resection |
Sato et al., 1995 [29] | DNFB, DNFB sensitization and CY pretreatment combined with BCG and nodal resection | Stages III and IV metastatic melanoma in patients | i.d. DNP-autologous melanoma injection | IFNγ producing CD8 T cells that killed DNP-melanoma only |
Sato et al., 1997 [27] | DNFB, DNFB sensitization and CY pretreatment combined with BCG and nodal resection | Stages III and IV metastatic melanoma in patients | i.d. DNP-autologous melanoma injection | DNP-specific T-cells recognize only hapten-modified melanoma |
Berd et al., 1997 [28] | DNFB, DNFB sensitization and CY pretreatment combined with BCG and nodal resection | Stage III metastatic melanoma postnodal resection in patients | i.d. DNP-autologous melanoma injection | 5-year 45% relapse-free and 58% overall survival (62 patients) |
Berd et al., 2001 [26] | DNFB, DNFB sensitization and CY pretreatment combined with BCG and nodal resection | Stage IV melanoma with pulmonary metastases in patients | i.d. DNP-autologous melanoma injection | 11/83 patients had responses to treatment, only 2 had complete response |
Manne et al., 2002 [25] | DNFB, DNFB sensitization and CY pretreatment combined with BCG and nodal resection | Stage III metastatic melanoma postnodal resection in patients | i.d. DNP-autologous melanoma injection | T-cell clones from DNP-vaccine patients with similar TCR VDJ peaks and CDR3 amino acid sequences |
Sojka et al., 2002 [31] | DNFB, CY pretreatment combined with BCG and nodal resection | 410.1 cells in Balb/c mice | s.c. DNP-410.1 injection | 40% relapse-free survival with DNP-vaccine versus 20% without DNP; CD4+, and CD8+ T cells, and IFNγ and TNFα important for survival. |
Berd et al., 2004 [24] | DNFB, DNFB sensitization and CY pretreatment combined with BCG and nodal resection | Stage III metastatic melanoma postnodal resection in patients | i.d. DNP-autologous melanoma injection | 5-year 44% overall survival (214 patients) |
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In situ haptenation | Fujiwara et al., 1984 [32] | TNCB, TNCB sensitization and CY pretreatment | X5563 cells in C3H/HeN mice | Intratumoral injection of TNCB | >50% primary tumor regression and secondary tumor resistance. Helper T-cells crucial |
Fujiwara et al., 1984 [33] | TNCB, TNCB sensitization and CY pretreatment | X5563 cells, MCH-1-A1 cells, and MCA-induced tumors in C3H/HeN mice | Intratumoral injection of TNCB | >50% primary tumor regression and secondary tumor resistance. Helper T-cells crucial |
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Epifocal hapten application | Klein 1969 [34] | TEIB and DNCB, N/A | BCC and SCC in patients | Topical hapten application on tumor | Reviews various complete tumor regression cases in various different cancers and patients. |
Truchetet et al., 1989 [113] | DNCB, N/A | Metastatic melanoma in patients | Topical DNCB application on tumor |
Reviews the use of DNCB to treat metastatic melanoma in the clinic and in case studies |
Strobbe et al., 1997 [35] | DNCB, DNCB sensitization on tumor and systemic DTIC | Recurrent melanoma in patients | Topical DNCB application on tumor | 25% complete response with combined DNCB and DTIC treatment |
von Nida and Quirk, 2003 [36] | DNCB, DNCB sensitization | Metastatic melanoma in patients | Topical DNCB application on tumor | Tumor control for 7 years in metastatic melanoma patient with DNCB application |
Herrmann et al., 2004 [114] | DNCB, DNCB sensitization | Merkel cell carcinoma in patients | Topical DNCB application on tumor | Complete tumor regression on scalp and CD3+ T-cell and CD28+, KP-1+ Macrophage infiltration |
Damian et al., 2009 [39] | DPCP, DPCP sensitization | Metastatic melanoma in patients | Topical DPCP application on tumor | Of 7 patients, many had slow growing tumors or tumor regression at DPCP application site |
Martiniuk et al., 2010 [38] | DPCP, DPCP sensitization | Metastatic melanoma in patients | Topical DPCP application on tumor | Role of Th17 cells in tumor regression |
Kim 2012 [40] | DPCP, DPCP sensitization | Metastatic melanoma in patients | Topical DPCP application on tumor | Regression of melanoma nodules for 18 weeks |
Wack et al., 2001 [42] | DNCB, DNCB sensitization on tumor and systemic DTIC | B16F17 cells in C57BL/6 mice | Topical DNCB application on tumor | 72% primary tumor regression and reduced pulmonary metastases |
Wack et al., 2002 [41] | DNCB, DNCB sensitization on tumor and systemic DTIC | B16F17 cells in C57BL/6 mice | Topical DNCB application on tumor | Repeat 2001 results, CD4+ and CD8+ T cells kill B16 in vitro and release IFNγ |
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Lu and Low 2002 [46] | Folate-FITC conjugate, BSA-FITC sensitization with adjuvant GPI-0100 and systemic IL-2 and IFNα | M109 cells in Balb/c mice | i.v. and i.p. injection folate-FITC conjugate | FITC coating of tumors. 100% overall survival after optimization with combined treatment; survive secondary challenges |
| Lu et al., 2005 [45] | Folate-FITC conjugate, BSA-FITC sensitization with adjuvant GPI-0100 and systemic IL-2 and IFNα | M109 cells in Balb/c mice | i.p. injection folate-FITC conjugate | NK-cell induced ADCC and Macrophage opsonization; CD4+ and CD8+ T-cells important. Complete tumor regression in 35 days |
Antigen-hapten administration | Lu et al., 2006 [44] | Folate-FITC conjugate, BSA-FITC sensitization with adjuvant GPI-0100 and systemic IL-2 and IFNα | M109 cells in Balb/c mice | i.p. injection folate-FITC conjugate | Preclinical pharmacokinetic and tissue distribution studies |
Lu et al., 2007 [43] | Folate-DNP conjugate, KLH-DNP sensitization with adjuvant GPI-0100 and systemic IL-2 and IFNα | M109 cells in Balb/c mice | i.p. injection folate-DNP conjugate | 60% cure-rate in mice |
Amato et al., 2013 [47] | EC17 folate-FITC conjugate, EC90 hapten fluorescein with adjuvant GPI-0100 | Renal cell carcinoma in patients | s.c. injection folate-FITC conjugate | Phase-1 Study, 1/28 patients had partial response, 15/28 had stable disease; side effects |
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