Chapter 14 - A novel bispecific antibody targeting EGFR and cMet is effective against EGFR inhibitor-resistant lung tumors

Abstract

Nonsmall cell lung cancer (NSCLC) can develop resistance to tyrosine kinase inhibitors (TKIs) through site mutations in EGFR (T790M) and activation of the cMet pathway. This chapter describes a bispecific EGFR-cMet antibody with multiple mechanisms of action. The researchers developed this antibody in NSCLC to inhibit the effects of EGFR mutations and cMet pathway activation. The developer named the antibody JNJ-61186372. This antibody blocks ligand-induced phosphorylation of EGFR and cMet, and this blockade provides more potent inhibition than the combination of single receptor-binding antibodies. In NSCLC tumor models, the therapeutic effects of JNJ-61186372 may be achieved through inhibition of signal/receptor downregulation and Fc-driven effector interactions. Antibody therapy can cause tumor regression. The therapeutic effect of concurrent use of JNJ-61186372 and a third-generation EGFR TKI were observed in a human lung xenograft tumor model. Treatment with JNJ-61186372 in mammals did not produce severe toxicity, and no common antibody drug side effects, such as skin rash, were observed. Bispecific EGFR-cMet antibodies have great potential in inhibiting EGFR mutation-induced drug resistance in NSCLC.