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Induction of protective immunity to RM‐1 prostate cancer cells with ALVAC‐IL‐2/IL‐12/TNF‐α combination therapy

Human prostate cancers characteristically express low levels of major histocompatibility complex (MHC) Class I, which makes it challenging to induce protective antitumor responses involving T cells. Here we demonstrate that a whole cell tumor vaccine can induce protective T cell immunity to a low MHC Class I‐expressing mouse prostate cancer cell line, RM‐1. ALVAC recombinant canarypox viruses encoding interleukin‐2, interleukin‐12 and tumor necrosis factor‐α were used to create therapeutic vaccines in 2 different ways. The RM‐1 cells were pre‐infected in vitro with the viruses prior to injection (pre‐infection vaccine) or the RM‐1 cells were injected alone, followed by the viruses (separate injection vaccine). The vaccines were each tested subcutaneously or intradermally. The pre‐infection vaccine resulted in 100% clearance of primary tumors, whereas intradermal delivery of the separate injection vaccine cleared 40–60% of primary tumors. Despite the highly efficient primary tumor clearance by the pre‐infection vaccine, only the separate injection vaccine generated protection upon rechallenge. Tumor‐free survival induced by the separate injection vaccine required natural killer (NK) cells, CD4+, and CD8+ T cells. None of these cells alone were sufficient to induce tumor‐free survival to the primary challenge, demonstrating an important cooperativity between NK cells and T cells. Secondary clearance of tumors also required NK and CD8+ T cells, but not CD4+ T cells. We report for the first time the generation of T cell immunity to the RM‐1 prostate cancer cell line, demonstrating that it is possible to generate protective T cell immunity to a MHC I‐low expressing tumor. © 2006 Wiley‐Liss, Inc.