PK313

PK313 is a TCR-mimicking bispecific T cell engager (TCE) developed by Aethon Therapeutics to target KRAS-amplified tumors. It specifically binds to kAMP.A2, a KRAS-derived peptide-MHC (pMHC) antigen presented by HLA-A*02:01, which is selectively overexpressed in tumors with KRAS gene amplification or those that have developed amplification as a resistance mechanism to KRAS inhibitors. By simultaneously binding to kAMP.A2 on tumor cells and the CD3 complex on T cells, PK313 facilitates the formation of immunological synapses and subsequent T cell-mediated cytotoxicity. Preclinical studies indicate that PK313 has high affinity and specificity, showing potent activity in KRAS-amplified models of gastroesophageal and lung cancers, particularly when used in combination with KRAS small molecule inhibitors.