Abstract
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.
Original language | English (US) |
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Pages (from-to) | 2632-2641 |
Number of pages | 10 |
Journal | International Journal of Cancer |
Volume | 119 |
Issue number | 11 |
DOIs | |
State | Published - Dec 1 2006 |
Keywords
- ALVAC
- NK cells
- Prostate cancer
- RM-1
- T cells