Generation of a safe and efficacious llama single-domain antibody fragment (vHH) targeting the membrane-proximal region of 4-1BB for engineering therapeutic bispecific antibodies for cancer

Abstract

A unique single-domain antibody was discovered that binds to the CRD4 domain of 4-1BB. When incorporated into a 4-1BB/PD-L1 bispecific (PM1003), we have shown the potent inhibition of PD-L1 activity with 4-1BB agonism upon cross-bridging with PD-L1 <i>in vitro</i>. Antitumor activity with minimal toxicity was found <i>in vivo</i>. Thus, PM1003 is a uniquely differentiating and next generation therapeutic agent for cancer therapy.