(AstraZeneca) AZD5863, a CLDN18.2 and CD3 binding T-cell engager, establishes a multi-faceted antitumour immune response and combines effectively with chemo-immunotherapy regimens

Abstract

Background

CLDN18.2 is a tetraspanin, highly expressed in gastric and pancreatic cancers. A CLDN18.2-targeting monoclonal antibody approach as monotherapy or in combination with chemotherapies has demonstrated benefit in gastric cancer [1,2]. AZD5863 is a CLDN18.2 and CD3-targeting T-cell engager (TCE), designed with high-affinity to human, cynomolgus monkey and mouse CLDN18.2 and low-affinity to human CD3. Gaining mechanistic insights into the mode of action of novel TCEs is critical to further their advancement into the clinic. Here, we investigated the pharmacodynamics of AZD5863 in preclinical models and assessed its combinability with chemo-immunotherapy regimens, relevant to the treatment of gastric cancer.