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Inhibition of tumor growth by recombinant vaccinia virus expressing GA733/CO17-1A/EpCAM/KSA/KS1-4 antigen in mice

Cancer Gene Therapy volume 9, pages 382–389 (2002)Cite this article

Abstract

The human colorectal carcinoma (CRC)-associated GA733 antigen (Ag), also named CO17-1A/EpCAM/KSA/KS1-4, has been a useful target in passive immunotherapy of CRC patients with monoclonal antibody (mAb) and in active immunotherapy with anti-idiotypic antibodies or with recombinant protein. These approaches have targeted single epitopes (monoclonal anti-GA733 antibodies and anti-idiotypic antibodies) or extracellular domain epitopes (recombinant protein), primarily by B cells. To determine whether a reagent that induces immunity to a larger number of both B- and T-cell epitopes might represent a superior vaccine, we analyzed the capacity of full-length GA733 Ag expressing multiple potentially immunogenic epitopes and encoded by recombinant vaccinia virus (VV GA733-2) to induce humoral, cellular, and/or protective immunity in mice. VV GA733-2 induced Ag-specific antibodies that reacted predominantly to unknown epitopes on the Ag and lysed Ag-positive CRC targets in conjunction with murine peritoneal macrophages as effector cells. Immunized mice developed Ag-specific, proliferative and delayed-type hypersensitive lymphocytes. VV GA733-2 inhibited growth of ras-transformed syngeneic tumor cells expressing the human GA733 Ag in mice. These results suggest the potential of VV GA733-2 as a candidate vaccine for patients with CRC, possibly in combination with recombinant GA733-2–expressing adenovirus, which has been shown to induce cytolytic antibodies and T cells as well as tumor protective effects in mice. The combined vaccine approach may be superior to the use of either vaccine alone in patients who are pre-immune to both viruses.

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Acknowledgements

This work was supported in part by Grants CA 10815, CA 60595, CA 74294, and CA 29797 from the National Institutes of Health, and a grant from Ajinomoto, Japan. We thank Dr Eva Gönczöl for critically reviewing this manuscript.

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Authors and Affiliations

  1. The Wistar Institute, Philadelphia, 19104, Pennsylvania, USA

    Jan Zaloudik, Weiping Li, Lutz Jacob, Rajasekharan Somasundaram, Hong Song, Tianqian Zhang, Jian Li & Dorothee Herlyn

  2. Transgene S.A., Strasbourg, France

    Marie Paule Kieny & Bruce Acres

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  1. Jan Zaloudik
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Correspondence to Dorothee Herlyn.

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Zaloudik, J., Li, W., Jacob, L. et al. Inhibition of tumor growth by recombinant vaccinia virus expressing GA733/CO17-1A/EpCAM/KSA/KS1-4 antigen in mice. Cancer Gene Ther 9, 382–389 (2002). https://doi.org/10.1038/sj.cgt.7700452

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