Journal article
Induction of protective immunity to RM-1 prostate cancer cells with ALVAC-IL-2/IL-12/TNF-α combination therapy
International journal of cancer, Vol.119(11), pp.2632-2641
2006
DOI: 10.1002/ijc.22220
PMID: 16991124
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-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.
Details
- Title: Subtitle
- Induction of protective immunity to RM-1 prostate cancer cells with ALVAC-IL-2/IL-12/TNF-α combination therapy
- Creators
- Julieann F GRANT - Medical Scientist Training Program, University of Iowa, Iowa City, IA, United StatesToshihisa IWASAWA - Department of Urology, University of Iowa, Iowa City, IA, United StatesHaley W SINN - Department of Urology, University of Iowa, Iowa City, IA, United StatesD. Robert SIEMENS - Department of Urology, University of Iowa, Iowa City, IA, United StatesThomas S GRIFFITH - Department of Urology, University of Iowa, Iowa City, IA, United StatesElizabeth B TAKACS - Department of Urology, University of Iowa, Iowa City, IA, United StatesTimothy L RATLIFF - Medical Scientist Training Program, University of Iowa, Iowa City, IA, United States
- Resource Type
- Journal article
- Publication Details
- International journal of cancer, Vol.119(11), pp.2632-2641
- Publisher
- Wiley-Liss; New York, NY
- DOI
- 10.1002/ijc.22220
- PMID
- 16991124
- ISSN
- 0020-7136
- eISSN
- 1097-0215
- Language
- English
- Date published
- 2006
- Academic Unit
- Obstetrics and Gynecology; Urology
- Record Identifier
- 9984051784102771
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