Abstract
We developed a CAR T therapeutic to treat solid tumors. Over 75% of solid tumors aberrantly express the transmembrane glycoprotein MUC1. More accurately, these tumors express the cleavage product, MUC1*, which we showed is the growth factor receptor form. The targeting head of our CAR T is a humanized antibody that binds an epitope on MUC1* that is not exposed on full-length MUC1. Expression of MUC1*, but not full-length MUC1, increases as tumor stage increases and also as cancers acquire drug resistance. All previous therapies that targeted full-length MUC1 have failed, presumably because as cancers progress, cleavage of MUC1 extra cellular domain increases and the targeted portion is shed from the cell surface. More recent CAR T therapeutics, such as those using 5E5, target aberrant O-linked glycans, which only exist on full-length MUC1. This approach would only enrich for the tumor-promoting MUC1* form.
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