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Human natural killer cell line modified with a chimeric immunoglobulin T-cell receptor gene leads to tumor growth inhibition in vivo

Cancer Gene Therapy volume 9, pages 390–398 (2002)Cite this article

Abstract

The gene transfer of tumor-specific chimeric immunoglobulin T-cell receptors (cIgTCRs) combining antibody-like specificity with the effector cell function could be an attractive tool in immunotherapy. In this study, we directed the human natural killer (NK) cell line YT to tumor cells by gene transfer of a cIgTCR with specificity against the human carcinoembryonic antigen (CEA). The cIgTCR was constructed of a CEA-specific humanized single-chain Fv antibody fragment fused to the IgG1 Fc domain and the CD3 ζ chain. YT cells were transfected with the cIgTCR gene by electroporation and cIgTCR-expressing cells were enriched by immunoaffinity purification. cIgTCR-expressing YT cells specifically lysed CEA+ colon carcinoma cell lines, which were resistant to the parental YT cell line. The lysis was not inhibited in the presence of soluble CEA. Receptor gene–modified YT cells retained their CEA-specific cytolytic activity after γ-irradiation in vitro and inhibited the tumor growth in vivo after adoptive transfer into NOD/SCID mice. This gene-modified NK cell line available in unlimited source might be useful in clinical immunotherapy of CEA+ cancer.

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Acknowledgements

This work was supported by a fellowship from the Medical Faculty of the Charité, Humboldt-University Berlin to TS and by a fellowship Rahel Hirsch from the Medical Faculty of the Charité, Humboldt-University Berlin to GP. We especially thank J Yodoi (Institute for Virus Research) for providing the cell line YT and K Bosslet (Behringwerke) for providing the cDNA of the V regions of the humanized mAb BW431/26. We thank I Fichtner (EPO) for help with the mice experiments and JA Schenk (MDC) for critical reading of the manuscript.

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  1. Department of Internal Medicine, Medical Oncology and Hematology, AG Molecular Gene and Immunotherapy, Humboldt-University Berlin, Charité Campus Mitte, Berlin, 10115, Germany

    Thomas Schirrmann & Gabriele Pecher

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  1. Thomas Schirrmann
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  2. Gabriele Pecher
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Correspondence to Gabriele Pecher.

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Schirrmann, T., Pecher, G. Human natural killer cell line modified with a chimeric immunoglobulin T-cell receptor gene leads to tumor growth inhibition in vivo. Cancer Gene Ther 9, 390–398 (2002). https://doi.org/10.1038/sj.cgt.7700453

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