Induction of protective immunity to RM-1 prostate cancer cells with ALVAC-IL-2/IL-12/TNF-alpha combination therapy
| Autor: | Julieann F. Grant, Timothy L. Ratliff, Thomas S. Griffith, Elizabeth B. Takacs, Haley W. Sinn, D. Robert Siemens, Toshihisa Iwasawa |
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| Rok vydání: | 2006 |
| Předmět: |
Male
Cancer Research Enzyme-Linked Immunosorbent Assay Major histocompatibility complex Natural killer cell Interleukin 21 Mice Cell Line Tumor MHC class I medicine Cytotoxic T cell Animals Antigen-presenting cell Mice Inbred BALB C biology business.industry Tumor Necrosis Factor-alpha Prostatic Neoplasms Viral Vaccines Interleukin-12 medicine.anatomical_structure Oncology Immunology Interleukin 12 biology.protein business CD8 Cell Division |
| Zdroj: | International journal of cancer. 119(11) |
| ISSN: | 0020-7136 |
| Popis: | 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-alpha 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. |
| Databáze: | OpenAIRE |
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