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

Julieann F. Grant, Toshihisa Iwasawa, Haley W. Sinn, D. Robert Siemens, Thomas S. Griffith, Elizabeth B. Takacs, Timothy L. Ratliff

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

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 languageEnglish (US)
Pages (from-to)2632-2641
Number of pages10
JournalInternational Journal of Cancer
Volume119
Issue number11
DOIs
StatePublished - Dec 1 2006

Keywords

  • ALVAC
  • NK cells
  • Prostate cancer
  • RM-1
  • T cells

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