Human epidermal growth factor receptor 2 and Cluster of differentiation 3 (HER2/CD3)

The HER2 and CD3 dual target represents a therapeutic strategy utilizing bispecific antibodies to treat HER2-overexpressing malignancies. Human epidermal growth factor receptor 2 (HER2), also known as ERBB2, is a receptor tyrosine kinase that plays a critical role in cell growth and differentiation; its overexpression is a well-documented driver in breast, gastric, and other solid tumors (UniProt P04626). Cluster of differentiation 3 (CD3) is a multi-subunit protein complex found on T-cells that is essential for T-cell receptor signaling and activation (UniProt P07766). Bispecific antibodies targeting both HER2 and CD3 function by physically bridging T-cells to tumor cells, creating an artificial immunological synapse (PubMed 31515463). This proximity-induced activation triggers the release of cytotoxic granules, such as perforins and granzymes, leading to the direct lysis of HER2-positive cancer cells independent of MHC restriction (PubMed 28807231). This mechanism is designed to bypass immune evasion and enhance the potency of anti-HER2 therapy in patients who may be resistant to standard monoclonal antibodies.

Other names

ERBB2 and CD3HER2-CD3HER2/neu and CD3ERBB2/CD3HER2 x CD3HER2/CD3 BiTEHER2-T-cell engager

Bispecific T-cell engagement: simultaneously binding to HER2 on tumor cells and CD3 on T-cells to induce T-cell mediated lysis of the target cancer cells.