E. Bromley, R. Waitz, S. Wang
2011
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Journal of clinical oncology : official journal of the American Society of Clinical Oncology
Abstract
e13034 Background: Talaporfin sodium (TS) is a light-activated, locally cytoreductive drug in Phase 3 clinical trials for several different cancers. It is activated intratumorally with a thin, flexible LED array. TS treatment has been shown in preclinical studies to activate CD8+-dependent anti-tumor immunity in a model of metastatic breast cancer. Anti-CTLA4 antibody is an immunotherapy that acts by suppressing negative regulation of immune effectors. It has recently completed a successful Phase 3 clinical trial in melanoma patients in which it was shown to prolong survival.TS and anti-CTLA4 antibody have great potential to synergistically reduce primary tumor burden and generate systemic anti-tumor immunity. METHODS This study examined combination treatment with these two therapies in a murine prostate cancer tumor model (C57BL/6 + TRAMP C2). A large, established tumor on the left side of each mouse was treated with light-activated TS (or light-only control). One day after treatment, mice were injected intradermally with 0.5 x 106 TRAMP C2 cells on the opposite flank. Anti-CTLA4 (or vehicle control) was given on days 1, 4, 7 and 10. Progression of the untreated tumor was measured. RESULTS Growth of untreated tumors was prevented or significantly delayed in 55% and 33% of combination-treated animals, respectively (n = 9). In addition, contralateral tumor growth was prevented in 1 of 9 animals given talaporfin sodium alone while another animal's tumor showed growth delay. None of the untreated controls or anti-CTLA4 only animals showed a similar response. Individual combination-treated mice with delayed tumor growth often showed an atypical tumor growth curve in which progression either tapered off or began to reverse between 30 and 40 days post treatment. CONCLUSIONS Reduction of tumor using local treatment with a light-activated drug could potentiate the anti-tumor immune response resulting from anti-CTLA4 treatment and prevent growth of secondary tumors in a preclinical prostate cancer model.