huMNC2-CAR-CD28

huMNC2-CAR-CD28 is an informal shorthand referring to CD28-containing chimeric antigen receptor (CAR) T-cell therapies developed by Minerva Biotechnologies, specifically huMNC2-CAR28 (huMNC2-CD28-CD3ζ) and huMNC2-CAR22 (huMNC2-CD28-CD3ζ-1XX). These autologous CAR T-cell therapies are engineered to target MUC1* (MUC1-star), a tumor-associated cleaved form of mucin 1 that acts as a growth factor receptor on solid tumors, particularly metastatic breast cancer. The constructs utilize a humanized single-chain variable fragment (scFv) derived from the MNC2 antibody as the targeting head, coupled with a CD28 co-stimulatory domain. The huMNC2-CAR22 variant additionally incorporates '1XX' mutations (tyrosine-to-phenylalanine substitutions in the ITAM2 and ITAM3 domains of CD3ζ) to slow CAR T-cell signaling, reduce exhaustion, and enhance in vivo persistence and the killing of low-antigen-expressing tumor cells. huMNC2-CAR22 is being evaluated in a Phase I/II clinical trial (NCT04020575) for the treatment of metastatic breast cancer.

Other names

MUC1*-CAR-1XXhuMNC2-CAR-CD28huMNC-2-CAR-CD28huMNC 2-CAR-CD28huMNC2-CD28-CD3ζhuMNC2-CD28-CD3ζ-1XX