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Prostate Cancer Prostatic Dis. 2013 Jun;16(2):123-31, S1. doi: 10.1038/pcan.2012.49. Epub 2013 Jan 8.

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

Author information

1
Center for Cell and Gene Therapy, Baylor College of Medicine, The Methodist Hospital, Texas Children's Hospital, Houston, TX 77030, USA.

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.

PMID:
23295316
PMCID:
PMC3883310
DOI:
10.1038/pcan.2012.49
[Indexed for MEDLINE]
Free PMC Article

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