UBIQUITINATION-LACKING CHIMERIC ANTIGEN RECEPTOR AND USE THEREOF

    公开(公告)号:US20220280566A1

    公开(公告)日:2022-09-08

    申请号:US17603937

    申请日:2019-10-31

    Abstract: The present invention provides a chimeric antigen receptor, which includes: an extracellular domain, a transmembrane domain, and an intracellular domain connected in sequence. The extracellular domain includes an antigen recognition region; the intracellular domain includes a costimulatory signaling region and a CD3ζ intracellular region that are connected in sequence, to form a costimulatory signaling region-CD3ζ intracellular region; and the costimulatory signaling region-CD3ζ intracellular region is a polypeptide formed by mutation of lysine in a wild-type costimulatory signaling region-CD3ζ intracellular region into arginine. The present invention provides a method for optimization and modification of CAR-T, in which all lysine sites in an intracellular segment of CAR are mutated into arginine, thereby blocking ubiquitination modification of the CAR after antigen challenge. This strategy is applicable to different CARs and changing different intracellular costimulatory domains, and in particular provides a solution to the problem of poor proliferation of CAR-T in solid tumors.

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