Minerva and City of Hope Open Trial Targeting CAR T for Metastatic Breast Cancer

A first, in-human trial of huMNC2-CAR44 T cells (NCT04020575) targeting the tumor-associated form of MUC1, called MUC1* (muk 1 star), has opened at City of Hope, Duarte, CA.

MUC1* is the transmembrane cleavage product that is a growth factor receptor that drives growth of an estimated 93% of breast cancers. The antibody that targets Minerva Biotechnologies Corporation’s CAR T to the tumor binds to an ectopic site that is only exposed after cleavage and release of the tandem repeat domain. Other attempts at targeting MUC1 with antibodies, ADCs, or CAR Ts have targeted the tandem repeat domain, which is cleaved in the tumor microenvironment and shed from the cell surface. The huMNC2-CAR44 therapy was developed by Minerva.

The targeting head of the CAR, the antibody MNC2, recognizes a unique conformation of MUC1 after cleavage by a specific enzyme in the tumor microenvironment. “The ability of our antibody to bind specifically to the cancerous form of MUC1 without binding to MUC1 on normal tissues is a real breakthrough,” said Dr. Cynthia Bamdad, CEO of Minerva Biotechnologies.

“Demonstration of safety and early signs of efficacy of huMNC2-CAR44 represent a significant milestone for Minerva. We have a broad, deep pipeline that includes next generation CAR Ts, with enhanced in vivo persistence, and the ability to target cells with much lower antigen density, allowing us to challenge the persistence issues seen elsewhere in the field. We can now progress these to the clinic with increased confidence. We are also developing therapeutics that target the onco-embryonic growth factor, NME7, that activates the MUC1* growth factor receptor across many different types of solid tumors and the preclinical results are very encouraging,” said Minerva Chief Business Officer, Michael Crowther.