Differential patterns of cell surface marker expression in clinically relevant subgroups of non-small cell lung cancer.

Abstract

e20553 Background: Antibody-drug conjugates (ADC) and bispecific antibodies have an increasing role in solid tumors including thoracic malignancies. In the present work, we examine untargeted proteomic data for non-small cell lung cancer (NSCLC) from clinical proteomic tumor analysis consortium (CPTAC) datasets to determine patterns of protein expression for cell surface targets of ADCs and bispecific antibodies that have entered clinical trials for NSCLC. Methods: We compare quantified levels of protein expression in tumors and normal adjacent tissue to identify proteins that are up-regulated in tumor tissues. Criteria for up-regulation were defined as Log 2 (fold-change) >1 (tumor/normal), with Bonferroni-adjusted p-value from Wilcox rank-sum test <0.01. Results: We report that targets including MET, MUC1, NECTIN4, and SLC34A2 (NaPi2b) are up-regulated in EGFR-mutant lung adenocarcinoma relative to adjacent lung tissue, and that CD38 and NECTIN4 are up-regulated for KRAS-mutant lung adenocarcinoma relative to adjacent tissue. We also report up-regulation of CD276 (B7H3), CD38, NECTIN4, PTK7, and TPBG (5T4) in squamous cell carcinoma relative to adjacent tissue. Conclusions: Of these suggested targets, only MET has been successfully exploited with therapeutic success in EGFR-mutant NSCLC (Amivantimab: EGFRxMET bispecific antibody). Agents directed at the other suggested targets have yet to advance beyond early phase clinical trials for NSCLC. Our results showing over-expression of particular cell surface targets in specific tumor subsets suggests to us that these agents in early phase trials may ultimately be most effective in specific clinically-relevant subsets of NSCLC patients.