MUC1-C

Class

Allogeneic CAR-T cell therapy (Poseida Therapeutics)

Pathway

MUC1-C-directed T-cell cytotoxicity; includes a rimiducid-controlled safety switch

MUC1-C is the cytoplasmic subunit of mucin 1, a transmembrane glycoprotein normally expressed at low levels on the apical surface of epithelial cells, where it contributes to barrier protection. In many carcinomas, MUC1 is markedly overexpressed and aberrantly processed, and its C-terminal subunit, MUC1-C, translocates into the nucleus and other intracellular compartments, where it activates signaling programs that support tumor cell proliferation, resistance to programmed cell death, and transition toward a more invasive cellular state. This altered pattern of expression and localization distinguishes tumor cells from normal tissue sufficiently to support targeted therapies. Two distinct approaches to targeting MUC1-C are represented here: an antibody-drug conjugate, which uses an antibody to selectively deliver a cytotoxic payload to MUC1-C-expressing cells, and a chimeric antigen receptor (CAR) T-cell therapy, in which immune cells are engineered to recognize MUC1-C and kill tumor cells directly. Because this CAR-T product is allogeneic, meaning the T cells originate from a healthy donor rather than the patient being treated, it is designed to be manufactured in advance rather than individually for each patient. The engineered cells also carry a molecular safety switch that can be triggered by a separate small molecule to eliminate them if serious toxicity develops, offering a way to control how long the cells persist in the body.