Targeting MUC1* with CAR T Cells: A Novel Approach to Solid Tumor Therapy

The aim is to create a CAR T cell therapy that targets MUC1*, a cleavage product of MUC1, to treat solid tumors more effectively. Unlike previous treatments that focused on full-length MUC1, this approach addresses tumor heterogeneity and the microenvironment. The study found that MUC1* expression increases with tumor progression and lacks O-glycosylation sites, which are targeted by therapies like 5E5. The research led to the development of cancer-specific MUC1* antibodies, with huMNC2-CAR44 T cells showing promise for treating breast and ovarian cancers. The therapy is set to undergo human trials pending regulatory approval, with testing expected to start in mid-2018.

For the experimental procedures, anti-MUC1* CARs were produced and introduced into human T cells. A total of 60 CARs were evaluated in vitro for cytokine release and cell killing against MUC1*-positive cancer cells. Various methods were used to measure co-culture killing. In animal models, MUC1*-positive tumors were implanted and treated with human anti-MUC1* CAR T cells. Tumor growth was monitored over 60 days using IVIS technology.

New findings from human tissue studies support the safety and efficacy of the anti-MUC1* CAR T therapy. The huMNC2-CAR44 was selected based on its performance in human tissue studies, in vitro tests, and in vivo experiments. The in vivo results showed that huMNC2-CAR44 T cells significantly inhibited tumor growth, with Kaplan-Meier curves indicating no tumor-related deaths in the treated group at Day 61, compared to the control groups. The average IVIS measurements for the CAR T treated group were significantly lower than those for the control groups, with some mice showing no detectable tumor or very low tumor levels.