NRXN1 as a novel potential target of antibody-drug conjugates for small cell lung cancer
Takuma Yotsumoto, Keita Maemura, Kousuke Watanabe, Yosuke Amano, Yōko Matsumoto, Koichi Zokumasu, Takahiro Ando, Masanori Kawakami, Hidenori Kage, Jun Nakajima, Yutaka Yatomi, Takahide Nagase, Daiya Takai
Abstract
// Takuma Yotsumoto 1 , Keita Maemura 2 , Kousuke Watanabe 2 , 3 , Yosuke Amano 2 , Yoko Matsumoto 2 , Koichi Zokumasu 2 , Takahiro Ando 2 , Masanori Kawakami 2 , Hidenori Kage 2 , Jun Nakajima 1 , Yutaka Yatomi 3 , Takahide Nagase 2 and Daiya Takai 3 1 Department of Thoracic Surgery, The University of Tokyo Graduate School of Medicine, Tokyo, Japan 2 Department of Respiratory Medicine, The University of Tokyo Graduate School of Medicine, Tokyo, Japan 3 Department of Clinical Laboratory, The University of Tokyo Hospital, Tokyo, Japan Correspondence to: Daiya Takai, email: [email protected] Takuma Yotsumoto, email: [email protected] Keywords: antibody-drug conjugates; small cell lung cancer; novel molecular targets; NRXN1; cell adhesion molecule Received: June 23, 2020     Accepted: August 05, 2020     Published: September 29, 2020 ABSTRACT Small cell lung cancer (SCLC) is a high-grade malignancy, and treatment strategies have not changed for decades. In this study, we searched for novel targets for antibody-drug conjugate (ADC) therapy for SCLC. We identified transmembrane proteins overexpressed specifically in SCLC with little or no expression in normal tissues and decided to focus on the cell adhesion molecule neurexin-1 (NRXN1). The cell surface overexpression of NRXN1 was confirmed using flow cytometry in SCLC cell lines (SHP77 and NCI-H526). The combination of a primary anti-NRXN1 monoclonal antibody and a secondary ADC exhibited anti-tumor activity in SCLC cell lines. Moreover, the knockout of NRXN1 in SHP77 cells resulted in a loss of the anti-tumor activity of NRXN1-mediated ADC therapy. Thus, NRXN1 could be a novel target for ADC therapy for the treatment of SCLC that is worth further research.