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. 2015 Apr 13;12(6):656–668. doi: 10.1038/cmi.2015.28

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Copyright © 2015 Chinese Society of Immunology and The University of Science and Technology

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Genetic modification of γδ T cells for adoptive therapy approaches to cancer. (a) γδ T cells can be redirected to kill cancer cells using a chimeric antigen receptor (CAR) made from an antibody that targets a tumour-specific molecule at the cancer cell surface. (b) αβ T cells can be redirected to kill cancer cells by transducing them with a cancer-specific αβ TCR. Such αβ TCR gene transfer could result in the expression of up to four different αβ TCRs at the T cell surface: (i) the endogenous TCR; (ii) the transduced TCR; (iii) a hybrid TCR consisting of the endogenous TCRα chain paired with the transduced TCRβ chain; and (iv) endogenous TCRβ chain paired with the transduced TCRα chain. Neither hybrid will have undergone the rigours of thymic selection and therefore these TCRs have the potential of being autoreactive. (c) Transduction of γδ T cells with an αβ TCR provides a means of circumventing the potential mispairing problem seen in b.