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Immune responses against PSMA after gene-based vaccination for immunotherapy – A: results from immunizations in animals

Cancer Gene Therapy volume 13, pages 436–444 (2006)Cite this article

Abstract

Two plasmid DNA vaccines, encoding either products that are retained in the cytosol and degraded in the proteasome (tVacs; hPSMAt), or secreted proteins (sVacs; hPSMAs) were evaluated for stimulation of cytotoxic cell or antibody responses. Immunization with both vectors led to generation of cell cytotoxicity providing granulocyte-macrophage colony-stimulating factor was administered with the vaccine. Spleen cells from animals immunized with hPSMAt demonstrated stronger cytotoxicity to the target cells. Priming with a vector that encoded a xenogeneic protein (hPSMAt; ‘xenogeneic’ construct) and boosting with a vector that encoded an autologous protein (rPSMAt; ‘autologous’ construct) gave the best protection against tumor challenge. Immunization with tVacs did not lead to formation of antibodies to the target protein as detected by Western blot or ELISA, while immunization with sVacs or with the protein did. Antibodies were of mixed Th1–Th2 isotype. Priming with tVacs and boosting with protein also resulted in antibody formation, but in this case the antibodies were from the cytotoxic, Th1 isotype. The best strategy to obtain a strong cellular cytotoxic response, therefore, seems to be gene-based vaccinations with tVacs, priming with the ‘xenogeneic’ and boosting with the ‘autologous’ constructs. When cytotoxic antibody production is the goal, priming should be performed with the tVacs while boosting with the protein.

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Acknowledgements

This work was supported in part by Grant N00014-00-1-0787 from the Office of Naval Research. This work was also supported in part by Award No DAMD17-02-1-0239. The US Army Medical Research Acquisition Activity, 820 Chandler Street, Fort Detrick, MD 21702-5014 is the awarding and administering acquisition office.

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  1. Department of Medicine, Tumor Immunology Laboratory, The George Washington University Medical Center, Washington, DC, USA

    M Mincheff, S Zoubak & Y Makogonenko

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Correspondence to M Mincheff.

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Mincheff, M., Zoubak, S. & Makogonenko, Y. Immune responses against PSMA after gene-based vaccination for immunotherapy – A: results from immunizations in animals. Cancer Gene Ther 13, 436–444 (2006). https://doi.org/10.1038/sj.cgt.7700914

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