Nat Biomed Eng, 2023

Control of the antitumour activity and specificity of CAR T cells via organic adapters covalently tethering the CAR to tumour cells

On-target off-tumour toxicity limits the anticancer applicability of chimaeric antigen receptor (CAR) T cells. Here we show that the tumour-targeting specificity and activity of T cells with a CAR consisting of an antibody with a lysine residue that catalytically forms a reversible covalent bond with a 1,3-diketone hapten can be regulated by the concentration of a small-molecule adapter. This adapter selectively binds to the hapten and to a chosen tumour antigen via a small-molecule binder identified via a DNA-encoded library. The adapter therefore controls the formation of a covalent bond between the catalytic antibody and the hapten, as well as the tethering of the CAR T cells to the tumour cells, and hence the cytotoxicity and specificity of the cytotoxic T cells, as we show in vitro and in mice with prostate cancer xenografts. Such small-molecule switches of T-cell cytotoxicity and specificity via an antigen-independent 'universal' CAR may enhance the control and safety profile of CAR-based cellular immunotherapies.

Stepanov AV, Xie J, Zhu Q, Shen Z, Su W, Kuai L, Soll R, Rader C, Shaver G, Douthit L, Zhang D, Kalinin R, Fu X, Zhao Y, Qin T, Baran PS, Gabibov AG, Bushnell D, Neri D, Kornberg RD, Lerner RA

IBCH: 10901
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Кол-во цитирований на 05.2024: 1
Данные статьи проверены модераторами 2023-10-15

Список научных проектов, где отмечена публикация

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