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- W4313351808 abstract "Abstract Immunotherapy with innate immune cells has recently evoked a broad interest as a novel treatment option for cancer patients. γ9δ2T-cells are an emerging innate cell population with strong anti-tumor-reactivity and a promising candidate for immune interventions. Especially γ9δ2T-cell receptors (TCR) which recognize a broad panel of tumor cells with high avidity are clinically attractive since αβT-cells can be efficiently redirected against a variety of tumor cells by introducing a γ9δ2TCR. Here we demonstrate that distinct γ9δ2TCRs mediate different functional avidities and present the concept of combinatorial-γδTCR-chain exchange (CTE) as an efficient method to create γ9δ2TCRs that mediate strong anti-tumor-responses. Thereby γ9- and δ2-chains derived from individual γ9δ2T-cell clones are newly combined allowing the design of γ9δ2TCRs that mediate a higher functional avidity against a broad tumor cell panel in vitro and in vivo when compared to a reference γ9δ2TCR. We furthermore demonstrate that this phenomenon is selectively caused by differences in the CDR3-domains of γ9- and δ2-chain. Accordingly, alanine-scanning-mutations were performed and elucidated important residues within the CDR3 sequence and stress the impact of the CDR3 length for optimal γ9δ2TCR function. This knowledge allowed improving tumor-control by engineered T-cells not only in vitro but also in vivo in a humanized mouse model." @default.
- W4313351808 created "2023-01-06" @default.
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- W4313351808 date "2012-05-01" @default.
- W4313351808 modified "2023-10-01" @default.
- W4313351808 title "Avidity maturation of γ9δ2T-cell receptor engineered T-cells by CDR3 modulation (162.37)" @default.
- W4313351808 doi "https://doi.org/10.4049/jimmunol.188.supp.162.37" @default.
- W4313351808 hasPublicationYear "2012" @default.
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