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Anti-γδ TCR antibody-expanded γδ T cells: a better choice for the adoptive immunotherapy of lymphoid malignancies

Cellular & Molecular Immunology volume 9, pages 34–44 (2012)Cite this article

Abstract

Cell-based immunotherapy for lymphoid malignancies has gained increasing attention as patients develop resistance to conventional treatments. γδ T cells, which have major histocompatibility complex (MHC)-unrestricted lytic activity, have become a promising candidate population for adoptive cell transfer therapy. We previously established a stable condition for expanding γδ T cells by using anti-γδ T-cell receptor (TCR) antibody. In this study, we found that adoptive transfer of the expanded γδ T cells to Daudi lymphoma-bearing nude mice significantly prolonged the survival time of the mice and improved their living status. We further investigated the characteristics of these antibody-expanded γδ T cells compared to the more commonly used phosphoantigen-expanded γδ T cells and evaluated the feasibility of employing them in the treatment of lymphoid malignancies. Slow but sustained proliferation of human peripheral blood γδ T cells was observed upon stimulation with anti-γδ TCR antibody. Compared to phosphoantigen-stimulated γδ T cells, the antibody-expanded cells manifested similar functional phenotypes and cytotoxic activity towards lymphoma cell lines. It is noteworthy that the anti-γδ TCR antibody could expand both the Vδ1 and Vδ2 subsets of γδ T cells. The in vitro-expanded Vδ1 T cells displayed comparable tumour cell-killing activity to Vδ2 T cells. Importantly, owing to higher C–C chemokine receptor 4 (CCR4) and CCR8 expression, the Vδ1 T cells were more prone to infiltrate CCL17- or CCL22-expressing lymphomas than the Vδ2 T cells. Characterizing the peripheral blood γδ T cells from lymphoma patients further confirmed that the anti-γδ TCR antibody-expanded γδ T cells could be a more efficacious choice for the treatment of lymphoid malignancies than phosphoantigen-expanded γδ T cells.

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Acknowledgements

This work was supported by two grants (No. 2006AA02Z480 and No. 2007AA021109) from the National High Technology Research and Development Program (863 Program), and one grant (No. 30972776) from the National Natural Science Foundation of China.

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  1. Department of Immunology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, National Key Laboratory of Medical Molecular Biology, Beijing, China

    Jianhua Zhou, Ning Kang, Lianxian Cui, Denian Ba & Wei He

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Correspondence to Ning Kang or Wei He.

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Zhou, J., Kang, N., Cui, L. et al. Anti-γδ TCR antibody-expanded γδ T cells: a better choice for the adoptive immunotherapy of lymphoid malignancies. Cell Mol Immunol 9, 34–44 (2012). https://doi.org/10.1038/cmi.2011.16

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