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Open Access Highly Accessed Research article

Systemic treatment with CAR-engineered T cells against PSCA delays subcutaneous tumor growth and prolongs survival of mice

Victoria Hillerdal, Mohanraj Ramachandran, Justyna Leja and Magnus Essand*

Author Affiliations

Department of Immunology, Genetics and Pathology, Rudbeck Laboratory, Uppsala University SE-75185 Uppsala, Sweden

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BMC Cancer 2014, 14:30  doi:10.1186/1471-2407-14-30

Published: 18 January 2014

Abstract

Background

Adoptive transfer of T cells genetically engineered with a chimeric antigen receptor (CAR) has successfully been used to treat both chronic and acute lymphocytic leukemia as well as other hematological cancers. Experimental therapy with CAR-engineered T cells has also shown promising results on solid tumors. The prostate stem cell antigen (PSCA) is a protein expressed on the surface of prostate epithelial cells as well as in primary and metastatic prostate cancer cells and therefore a promising target for immunotherapy of prostate cancer.

Methods

We developed a third-generation CAR against PSCA including the CD28, OX-40 and CD3 ζ signaling domains. T cells were transduced with a lentivirus encoding the PSCA-CAR and evaluated for cytokine production (paired Student’s t-test), proliferation (paired Student’s t-test), CD107a expression (paired Student’s t-test) and target cell killing in vitro and tumor growth and survival in vivo (Log-rank test comparing Kaplan-Meier survival curves).

Results

PSCA-CAR T cells exhibit specific interferon (IFN)-γ and interleukin (IL)-2 secretion and specific proliferation in response to PSCA-expressing target cells. Furthermore, the PSCA-CAR-engineered T cells efficiently kill PSCA-expressing tumor cells in vitro and systemic treatment with PSCA-CAR-engineered T cells significantly delays subcutaneous tumor growth and prolongs survival of mice.

Conclusions

Our data confirms that PSCA-CAR T cells may be developed for treatment of prostate cancer.

Keywords:
CAR T cells; PSCA; Genetic engineering; Prostate cancer; Adoptive transfer