huMNC2-CAR44 + huMNC2-CAR22

**huMNC2-CAR44 + huMNC2-CAR22** is an autologous CAR T-cell therapy combination developed by Minerva Biotechnologies targeting the cleaved, growth factor receptor form of MUC1 known as **MUC1***, which is highly expressed on ~70-90% of solid tumors including breast cancers but not on full-length MUC1 in normal tissues, enabling tumor-selective targeting. **huMNC2-CAR44** uses a humanized MNC2 scFv with CD8 hinge/transmembrane, 4-1BB costimulatory, and CD3ζ signaling domains, with in vitro antigen stimulation; **huMNC2-CAR22** uses CD28 hinge/transmembrane/costimulatory domains and a modified CD3ζ with 1XX (Tyr-to-Phe mutations in ITAMs 2/3) for reduced exhaustion and improved persistence. Preclinical data show potent tumor killing in xenograft models, with CAR22 superior against low-antigen tumors; in a phase I/II trial (NCT04020575), patients receive either product (not combined) for metastatic breast cancer (MBC) subtypes requiring ≥30% MUC1* IHC positivity.[1][2][3][5]