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huMNC2-CD28-1XX (also known as huMNC2-CAR22) is an autologous chimeric antigen receptor (CAR) T-cell therapy developed by Minerva Biotechnologies for the treatment of MUC1*-positive solid tumors, particularly metastatic breast cancer. The CAR construct incorporates a humanized single-chain variable fragment (scFv) derived from the huMNC2 antibody, which specifically targets MUC1*, a tumor-associated cleaved form of mucin-1 that acts as a growth factor receptor. It features a CD28 costimulatory domain and a CD3ζ signaling domain containing the 1XX mutations (four tyrosine-to-phenylalanine mutations in ITAMs 2 and 3). These mutations restrict signaling to ITAM 1, slowing down T-cell activation to prevent exhaustion, enhance in vivo persistence, and improve the clearance of low-antigen-expressing tumor cells. huMNC2-CD28-1XX is currently being evaluated in a Phase I/II clinical trial.
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