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Bypassing tumor-specific and bispecific antibodies: triggering of antitumor immunity by expression of anti-FcγR scFv on cancer cell surface

Gene Therapy volume 8, pages 1721–1728 (2001)Cite this article

Abstract

We have developed a novel immunostimulatory molecule against tumor cells, composed of an anti-FcγRIII (CD16) scFv fused to the platelet-derived growth factor receptor (PDGFR) transmembrane region. This fusion molecule was stably expressed on the tumor cell surface and retained the ability of the parental antibody to bind soluble CD16. Tumor cells expressing anti-CD16 scFv triggered the release of IL-2 by Jurkat-CD16/γ cells and of TNFα by monocytes when co-cultured with these cells. Furthermore, NK cells could kill scFv-transfected HLA+ class I H1299 lung carcinoma tumor cells, but not the parental cells, indicating that anti-CD16 scFv tumor expression prevents the killer inhibitory receptor (KIR)-mediated inhibition of NK cell cytotoxicity. This anti-CD16 scFv tumor expression also enhanced tumor phagocytosis by IFNγ-activated macrophages, a mechanism known to induce a protective long-term adaptative immunity to tumors. In vivo Winn tests performed in SCID mice showed that the expression of anti-CD16 scFv on tumor cells, but not of the negative control anti-phOx scFv, prevented tumor cell growth. Thus, expression of FcR antibodies or other FcR-specific ligands on tumor cells represents a novel and potent antibody-based gene therapy approach, which may have clinical applications in cancer therapy.

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Acknowledgements

The authors wish to thank Dr A Aurias (Institut Curie, Paris, France) for providing access to fluorescence imaging system, Mrs C Chevalier (Institut Curie) for animal handling, Dr O Cochet (Exonhit, Paris, France) and Pr R Hawkins (Christie CRC Research Centre, Manchester, UK) for their help in the generation of the anti-CD16 scFv cDNA, Dr A Coronel (Institut Curie) for IFNγ-activated macrophage preparations, Pr F Belardelli (Istituto Superiore di Sanita, Rome, Italy) for advice on SCID mice, and Mrs Qi Cui for careful English reading of the manuscript. This work was supported by grants from the Institut Curie, the INSERM, the Fondation pour la Recherche Médicale (FRM) and the Association pour la Recherche contre le Cancer (ARC).

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  1. Laboratoire de Biotechnologie des Anticorps, Institut Curie, Paris, France

    N Gruel & JL Teillaud

  2. Unité INSERM U255, Institut Curie, Paris, France

    WH Fridman & JL Teillaud

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Gruel, N., Fridman, W. & Teillaud, J. Bypassing tumor-specific and bispecific antibodies: triggering of antitumor immunity by expression of anti-FcγR scFv on cancer cell surface. Gene Ther 8, 1721–1728 (2001). https://doi.org/10.1038/sj.gt.3301575

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