Combination immunotherapy of primary prostate cancer in a transgenic mouse model using CTLA-4 blockade

Arthur A. Hurwitz, Barbara A. Foster, Eugene D. Kwon, Tan Truong, Eugene M. Choi, Norman M. Greenberg, Maurice B. Burg, James P. Allison

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351 Scopus citations

Abstract

We have previously shown that antibodies to CTLA-4, an inhibitory receptor on T cells, can be effective at inducing regression of transplantable murine tumors. In this study, we demonstrate that an effective immune response against primary prostate tumors in transgenic (TRAMP) mice can be elicited using a strategy that combines CTLA-4 blockade and an irradiated tumor cell vaccine. Treatment of TRAMP mice at 14 weeks of age resulted in a significant reduction in tumor incidence (15% versus control, 75%), as assessed 2 months after treatment. Histopathological analysis revealed that treated mice had a lower tumor grade with significant accumulation of inflammatory cells in interductal spaces when treated with anti-CTLA-4 and a granulocyte-macrophage colony-stimulating factor-expressing vaccine. Vaccination of nontransgenic mice with this regimen resulted in marked prostatitis accompanied by destruction of epithelium, indicating that the immune response was, at least in part, directed against normal prostate antigens. These findings demonstrate that this combinatorial treatment can elicit a potent antiprostate response and suggest potential of this approach for treatment of prostate cancer.

Original languageEnglish (US)
Pages (from-to)2444-2448
Number of pages5
JournalCancer research
Volume60
Issue number9
StatePublished - May 1 2000

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Hurwitz, A. A., Foster, B. A., Kwon, E. D., Truong, T., Choi, E. M., Greenberg, N. M., Burg, M. B., & Allison, J. P. (2000). Combination immunotherapy of primary prostate cancer in a transgenic mouse model using CTLA-4 blockade. Cancer research, 60(9), 2444-2448.