Use of the Intracellular Signaling Domain of Receptor CD28H as a Component of Chimeric Antigen Receptors to Overcome Inhibition of Cytotoxic Lymphocytes by Checkpoint Receptors

Engineered chimeric antigen receptors (CARs) that are expressed in cytotoxic T cells and natural killer (NK) cells have been used to specifically target tumor cells. However, CAR-T and CAR-NK cells are still subject to downregulation by their inhibitory receptors after injection into patients.Scientists at NIAID have developed CAR constructs that overcome inhibition of NK cells by receptors for human major histocompatibility complex molecules HLA-E and HLA-C, based on in vitro studies. The CAR contains an antigen binding domain of receptor CD28 homolog (CD28H), a CD28H transmembrane domain (TM), a CD28H signaling domain, and other intracellular signaling domains, such as 2B4 (CD244) and CD3 zeta chain (CD3zeta). A variant of this CAR, in which the antigen binding domain of CD28H is replaced by a single-chain antibody variable region (scFv) that binds to CD19, rendered NK cells resistant to inhibition by HLA-E and HLA-C on CD19+ tumor cells.IC: NIAIDNIH Ref. No.: E-097-2020-0Advantages: Resistant to inhibition of NK cells or T cells by HLA-E and HLA-CManufacturing efficiencyCAR-NK can be developed without the need to genetic silencing of TCRApplications: Method of adoptive therapy where CAR-NK cell or CAR-T cell is the effector cellProvider Technology ID: 3408Updated On: Apr 20, 2020Date Published: Monday, April 20, 2020Patent Application: PCT/US2020/024985Patent Authority: PCTLead Inventor: Inventor IC: NIAIDNIAIDInventor...
Source: NIH OTT Licensing Opportunities - Category: Research Authors: Source Type: research