PK-E1

PK-E1 is a novel bispecific monoclonal antibody designed to target and block two immune checkpoint receptors: KIR3DL3 and PD-1. It was selected from a panel of bispecific antibodies for further characterization due to its ability to maintain binding and blocking of both targets, similar to another candidate PK-E3, but with more robust expression. PK-E1 has a specific structural conformation where the anti-PD-1 binding arm is in an IgG4 heavy chain format and the anti-KIR3DL3 binding arm is in an scFv format. It has demonstrated the ability to block KIR3DL3 on primary NK and NK92 cells, increasing the lysis of HHLA2+ target cells (HCC827 and K562). Additionally, PK-E1 exhibits an internalization mechanism by PD-1 expressing cells, similar to established PD-1 inhibitors like pembrolizumab and nivolumab, which is not observed in KIR3DL3 expressing cells. This dual-targeting approach aims to augment the anti-tumor effects seen with monotherapies by combining PD-1 blockade with KIR3DL3 inhibition, particularly in solid tumors.