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Recombinant vaccinia viruses expressing immunoglobulin variable regions efficiently and selectively protect mice against tumoral B-cell growth

Cancer Gene Therapy volume 8, pages 815–826 (2001)Cite this article

Abstract

The variable regions of the immunoglobulin (Ig) expressed on the surface of a malignant B cell can be considered tumor-specific antigens and, as such, could be targets for immunotherapeutic approaches. However, because until now the immunization procedures have been complex and have given only partial protection, it was necessary to find new methods of immunotherapy. Here, we present a successful method of vaccination against B-cell tumors in a murine model. We produced recombinant vaccinia viruses (rVV) expressing the heavy and the light chain of surface Ig of a patient's malignant B cells and we tested the ability of these rVV to protect immunized mice against tumor growth of transfectomas producing the same human Ig. The protection of the mice was complete and specific to the variable region of the immunizing heavy chain although specific lymphoproliferative and cytotoxic responses were not detectable in vitro. The protection was strictly dependent on the presence of CD4 T cells and asialo GM1+ cells. Furthermore, tumor protection clearly required γ-interferon and was partially inhibited by blocking the Fas–Fas ligand interaction. We also show, in a murine syngeneic model, that rVV expressing a poorly mutated Ig protects against the growth of Ig-producing tumor. Cancer Gene Therapy (2001) 8, 815–826

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Acknowledgements

Sémia BenAmmar-Ceccoli was supported by a fellowship from the Association de la Recherche contre le Cancer and the Ligue de Recherche contre le Cancer du Haut-Rhin et du Bas-Rhin. The research was supported by grants from the Association de la Recherche contre le Cancer and the Ligue Nationale Française de Recherche contre le Cancer.

We thank K. Dott and E. Lozay for technical assistance; S. Chouaib for helpful discussions; C. Benoist and D. Mathis for providing 14.4.4., H97, YTS177.9.6.1, YTS105.18.10, and R46A2 antibodies; E. Vivier for the antiasialo GM1 antibody; H. Yagita for the MFL1 mAb; and R. Drillien and D. Spehner for supplying BHK-21 cells and help in VVr purification.

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Authors and Affiliations

  1. Laboratoire d'Immunopathologie, Institut d'Immuno-hématologie, Hôpital Civil, Strasbourg, 67091, France

    Sémia BenAmmar-Ceccoli, Sophie Humblot, Rachel Crouzier, Jean Louis Pasquali & Thierry Martin

  2. Transgène, Strasbourg, 67082, France

    Bruce Acres & Marie-Paule Kieny

  3. Wistar Institute, Philadelphia, 19104, Pennsylvania, USA

    Dorothee Herlyn

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  1. Sémia BenAmmar-Ceccoli
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Correspondence to Thierry Martin.

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BenAmmar-Ceccoli, S., Humblot, S., Crouzier, R. et al. Recombinant vaccinia viruses expressing immunoglobulin variable regions efficiently and selectively protect mice against tumoral B-cell growth. Cancer Gene Ther 8, 815–826 (2001). https://doi.org/10.1038/sj.cgt.7700376

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