CD46

Class

Antibody-drug conjugate (MMAE payload)

Pathway

Fully human antibody targeting a tumor-selective epitope of CD46, conjugated to the microtubule inhibitor monomethyl auristatin E (MMAE)

CD46 is a cell-surface protein normally involved in regulating the complement system, an arm of innate immunity that can perforate and destroy cells identified as foreign or damaged. By binding and inactivating complement fragments deposited on the cell membrane, CD46 protects the body's own cells from complement-mediated injury. In several cancers, including certain prostate cancers and some hematologic malignancies, CD46 is expressed at unusually high density on the tumor cell surface, distinguishing it from the lower levels found on most normal tissues. This differential expression makes CD46 an attractive docking point for antibody-drug conjugates (ADCs), which pair an antibody that recognizes the target with a cytotoxic payload. In this design, a fully human antibody directed at a tumor-associated region of CD46 delivers monomethyl auristatin E (MMAE), a potent inhibitor of microtubule assembly, directly into the tumor cell after the antibody-CD46 complex is internalized. Once released inside the cell, MMAE disrupts the microtubule network required for cell division, halting mitosis and triggering programmed cell death. The overall strategy relies on CD46's relative overabundance on malignant cells to concentrate a systemically toxic drug where it is needed, while limiting exposure of normal tissue that expresses CD46 more sparingly.