Oncotarget

Research Papers:

NRXN1 as a novel potential target of antibody-drug conjugates for small cell lung cancer

Takuma Yotsumoto _, Keita Maemura, Kousuke Watanabe, Yosuke Amano, Yoko Matsumoto, Koichi Zokumasu, Takahiro Ando, Masanori Kawakami, Hidenori Kage, Jun Nakajima, Yutaka Yatomi, Takahide Nagase and Daiya Takai _

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Oncotarget. 2020; 11:3590-3600. https://doi.org/10.18632/oncotarget.27718

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Abstract

Takuma Yotsumoto1, Keita Maemura2, Kousuke Watanabe2,3, Yosuke Amano2, Yoko Matsumoto2, Koichi Zokumasu2, Takahiro Ando2, Masanori Kawakami2, Hidenori Kage2, Jun Nakajima1, Yutaka Yatomi3, Takahide Nagase2 and Daiya Takai3

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: dtakai-ind@umin.ac.jps
Takuma Yotsumoto,email: tyotsumoto-ths@umin.ac.jp

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.


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