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Basic Research

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

Prostate Cancer and Prostatic Diseases volume 16, pages 123–131 (2013)Cite this article

Subjects

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.

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Acknowledgements

JFV is supported by an Idea Development Award from the Department of Defense Prostate Cancer Research Program (no. W81XWH-11-1-0625). The research work was also supported by the Adrienne Helis Malvin Medical Research Foundation through its direct engagement in the continuous active conduct of medical research in conjunction with Baylor College of Medicine. MKB is supported by a Fayez Sarofim Chair.

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Authors and Affiliations

  1. Center for Cell and Gene Therapy, Baylor College of Medicine, The Methodist Hospital, Texas Children’s Hospital, Houston, TX, USA

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

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  1. C Sanchez
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  2. R Chan
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Correspondence to J F Vera.

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Sanchez, C., Chan, R., Bajgain, P. et al. Combining T-cell immunotherapy and anti-androgen therapy for prostate cancer. Prostate Cancer Prostatic Dis 16, 123–131 (2013). https://doi.org/10.1038/pcan.2012.49

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