Combining T-cell immunotherapy and anti-androgen therapy for prostate cancer

C. Sanchez, R. Chan, P. Bajgain, S. Rambally, G. Palapattu, M. Mims, C. M. Rooney, A. M. Leen, M. K. Brenner, J. F. Vera

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

Background:Prostate cancer remains a significant health problem for men in the Western world. Although treatment modalities are available, these do not confer long-term benefit and are accompanied by substantial side effects. Adoptive immunotherapy represents an attractive alternative to conventional treatments as a means to control tumor growth.Methods:To selectively target the tumor-expressed form of Muc1 we constructed a retroviral vector encoding a chimeric antigen receptor (CAR) directed against the aberrantly-expressed extracellular portion of Muc1 called the 'variable number of tandem repeats'.Results:We now demonstrate that T cells can be genetically engineered to express a CAR targeting the tumor-associated antigen Muc1. CAR-Muc1 T cells were able to selectively kill Muc1-expressing human prostate cancer cells. However, we noted that heterogeneous expression of the Muc1 antigen on tumor cells facilitated immune escape and the outgrowth of target-antigen loss variants of the tumor. Given the importance of androgen ablation therapy in the management of metastatic prostate cancer, we therefore also tested the value of combining conventional (anti-androgen) and experimental (CAR-Muc1 T cells) approaches. We show that CAR-Muc1 T cells were not adversely impacted by anti-androgen therapy and subsequently demonstrate the feasibility of combining the approaches to produce additive anti-tumor effects in vitro.Conclusions: Adoptive transfer of CAR-Muc1 T cells alone or in combination with other luteinizing hormone-releasing hormone analogs or antagonists should be tested in human clinical trials.

Original languageEnglish (US)
Pages (from-to)123-131
Number of pages9
JournalProstate Cancer and Prostatic Diseases
Volume16
Issue number2
DOIs
StatePublished - Jun 1 2013

Keywords

  • CAR T cells
  • combination therapy
  • immunotherapy
  • tumor immune escape

ASJC Scopus subject areas

  • Oncology
  • Urology
  • Cancer Research

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    Sanchez, C., Chan, R., Bajgain, P., Rambally, S., Palapattu, G., Mims, M., Rooney, C. M., Leen, A. M., Brenner, M. K., & Vera, J. F. (2013). Combining T-cell immunotherapy and anti-androgen therapy for prostate cancer. Prostate Cancer and Prostatic Diseases, 16(2), 123-131. https://doi.org/10.1038/pcan.2012.49