Signal-regulatory protein alpha (SIRPα) and Epithelial cell adhesion molecule (EpCAM) (SIRPα and EpCAM)

This target refers to the dual engagement of Signal-regulatory protein alpha (SIRPα) and Epithelial cell adhesion molecule (EpCAM), typically addressed by bispecific antibodies such as those in Apeximmune Therapeutics' Macrophage Engaging Bispecific Antibody (MEBA) platform. SIRPα is an inhibitory receptor expressed primarily on myeloid cells, including macrophages and dendritic cells, that interacts with CD47 on tumor cells to deliver a "don't eat me" signal, thereby suppressing phagocytosis. EpCAM, also known as tumor-associated antigen 2 (TAA2), is a cell surface glycoprotein highly overexpressed in various carcinomas and involved in cell-cell adhesion and signaling pathways like Wnt/beta-catenin. By simultaneously blocking the SIRPα-CD47 checkpoint and binding to EpCAM on tumor cells, therapeutic agents can specifically redirect and activate macrophages to engulf and destroy cancer cells through antibody-dependent cellular phagocytosis (ADCP). This dual-targeting approach aims to enhance the therapeutic index by focusing immune activation on the tumor microenvironment while minimizing systemic toxicity associated with broader checkpoint blockade.

Other names

CD172aSHPS-1BITMFRP84SIRP-alpha-1CD326TROP1TACSTD1GA733-2Gastrointestinal tumor-associated antigen 2Major gastrointestinal tumor-associated protein GA733-2

Bispecific engagement to block the SIRPα-CD47 inhibitory signal while simultaneously targeting EpCAM-positive tumor cells to induce macrophage-mediated phagocytosis (ADCP).