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

Research output: Contribution to journalArticle

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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
Externally publishedYes

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Immunotherapy
Transgenic Mice
Prostatic Neoplasms
Prostate
Neoplasms
Costimulatory and Inhibitory T-Cell Receptors
Prostatitis
Cancer Vaccines
Therapeutics
Granulocyte-Macrophage Colony-Stimulating Factor
Vaccination
Vaccines
Epithelium
Antigens
Antibodies
Incidence

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Hurwitz, A. A., Foster, B. A., Kwon, E. D., Truong, T., Choi, E. M., Greenberg, N. M., ... 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.

Combination immunotherapy of primary prostate cancer in a transgenic mouse model using CTLA-4 blockade. / Hurwitz, Arthur A.; Foster, Barbara A.; Kwon, Eugene D; Truong, Tan; Choi, Eugene M.; Greenberg, Norman M.; Burg, Maurice B.; Allison, James P.

In: Cancer Research, Vol. 60, No. 9, 01.05.2000, p. 2444-2448.

Research output: Contribution to journalArticle

Hurwitz, AA, Foster, BA, Kwon, ED, Truong, T, Choi, EM, Greenberg, NM, Burg, MB & Allison, JP 2000, 'Combination immunotherapy of primary prostate cancer in a transgenic mouse model using CTLA-4 blockade', Cancer Research, vol. 60, no. 9, pp. 2444-2448.
Hurwitz AA, Foster BA, Kwon ED, Truong T, Choi EM, Greenberg NM et al. Combination immunotherapy of primary prostate cancer in a transgenic mouse model using CTLA-4 blockade. Cancer Research. 2000 May 1;60(9):2444-2448.
Hurwitz, Arthur A. ; Foster, Barbara A. ; Kwon, Eugene D ; Truong, Tan ; Choi, Eugene M. ; Greenberg, Norman M. ; Burg, Maurice B. ; Allison, James P. / Combination immunotherapy of primary prostate cancer in a transgenic mouse model using CTLA-4 blockade. In: Cancer Research. 2000 ; Vol. 60, No. 9. pp. 2444-2448.
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