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Efficient transfer of PSA and PSMA cDNAs into DCs generates antibody and T cell antitumor responses in vivo

Cancer Gene Therapy volume 12, pages 540–551 (2005)Cite this article

Abstract

Gene therapy for prostate cancer may be realized through transduction of whole genes, such as PSA or PSMA, into immunotherapeutic dendritic cells (DCs). An oncoretroviral vector encoding human PSMA and a bicistronic oncoretroviral vector encoding human PSA and cell surface CD25 cDNAs were constructed. Remarkably, transfer of PSA/CD25 or PSMA cDNA during murine hematopoietic cell differentiation into DCs occurred with approximately 80% efficiency. In vitro, transduced DCs retained allostimulatory function and primed syngeneic T cells for tumor antigen-specific IFN-γ secretion. In test experiments designed to elucidate mechanisms in vivo, syngeneic recipients of transduced DCs had increased anti-human PSA antibody titers and tumor-specific CD8+ T cell IFN-γ secretion with no detectable immune response to CD25. Gene-modified DC recipients had increased protection from specific tumor challenge for at least 18 weeks post-vaccination. DC vaccination also protected both male and female recipients. Gene-modified DC vaccination mediated regression of established, specific gene-expressing, TRAMP-C1 prostate cancer cell tumors. These findings indicate that antibody and cellular responses generated through PSA and PSMA gene transfer into DC yielded protective immunity, thereby providing further preclinical support for the implementation of immuno-gene therapy approaches for prostate cancer.

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Acknowledgements

We thank Christopher Siatskas (OCI, UHN) for helpful discussions and critical reading of the manuscript along with JingMei Liu (UIC), Gangjian Qin (UIC), and John Campbell (OCI, UHN) for experimental assistance. This study was supported in part by the US Department of Defense Grant #DAMD17-00-1-0083 (to JAM).

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Authors and Affiliations

  1. Division of Experimental Therapeutics, Ontario Cancer Institute, Toronto, Ontario, Canada, M5G 2M1

    Jeffrey A Medin & Sheng-Ben Liang

  2. Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada, M5G 2M1

    Jeffrey A Medin

  3. Experimental Transplantation and Immunology Branch, National Cancer Institute, Bethesda, Maryland, 20892, USA

    Jeannie Whit-Shan Hou & Daniel H Fowler

  4. Section of Hematology/Oncology, Department of Medicine, University of Illinois at Chicago, Chicago, Illinois, 60607, USA

    Leslie S Kelley & David J Peace

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  1. Jeffrey A Medin
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Correspondence to Jeffrey A Medin.

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Medin, J., Liang, SB., Hou, JS. et al. Efficient transfer of PSA and PSMA cDNAs into DCs generates antibody and T cell antitumor responses in vivo. Cancer Gene Ther 12, 540–551 (2005). https://doi.org/10.1038/sj.cgt.7700810

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