A novel immune checkpoint siglec-15 antibody inhibits LUAD by modulating mφ polarization in TME

Xuejun Xiao; Yan Peng; Zheyue Wang; Louqian Zhang; Tingting Yang; Yangyang Sun; Yufeng Chen; Wenqing Zhang; Xinxia Chang; Wen Huang; Shuning Tian; Zhenqing Feng; Nabi Xinhua; Qi Tang; Yuan Mao

doi:10.1016/j.phrs.2022.106269

A novel immune checkpoint siglec-15 antibody inhibits LUAD by modulating mφ polarization in TME

Pharmacol Res. 2022 Jul:181:106269. doi: 10.1016/j.phrs.2022.106269. Epub 2022 May 20.

Authors

Xuejun Xiao¹, Yan Peng², Zheyue Wang², Louqian Zhang³, Tingting Yang², Yangyang Sun⁴, Yufeng Chen², Wenqing Zhang², Xinxia Chang², Wen Huang⁵, Shuning Tian⁶, Zhenqing Feng², Nabi Xinhua⁷, Qi Tang⁸, Yuan Mao⁹

Affiliations

¹ Department of Pharmacology, Xinjiang Medical University, Urumqi, China.
² NHC Key Laboratory of Antibody Technique, Nanjing Medical University, Nanjing, China; Jiangsu Province Engineering Research Center of Antibody Drug, Nanjing Medical University, Nanjing, China; Department of Pathology, Nanjing Medical University, Nanjing, China.
³ Department of Thoracic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China.
⁴ Department of Pathology, Changzhou No. 2 People's Hospital Affiliated with Nanjing Medical University, Changzhou, China.
⁵ Department of Oncology, The Fourth Affiliated Hospital of Nanjing Medical University, Nanjing, China.
⁶ NHC Key Laboratory of Antibody Technique, Nanjing Medical University, Nanjing, China; Jiangsu Province Engineering Research Center of Antibody Drug, Nanjing Medical University, Nanjing, China.
⁷ Department of Pharmacology, Xinjiang Medical University, Urumqi, China. Electronic address: Xinhua_xmu@126.com.
⁸ NHC Key Laboratory of Antibody Technique, Nanjing Medical University, Nanjing, China; Jiangsu Province Engineering Research Center of Antibody Drug, Nanjing Medical University, Nanjing, China; Department of Pathology, Changzhou No. 2 People's Hospital Affiliated with Nanjing Medical University, Changzhou, China. Electronic address: qitang@njmu.edu.cn.
⁹ Department of Oncology, The Fourth Affiliated Hospital of Nanjing Medical University, Nanjing, China; Department of Oncology, Geriatric Hospital of Nanjing Medical University, Nanjing, China; Department of Thoracic Surgery, Nanjing Medical University Affiliated Cancer Hospital, Nanjing, China. Electronic address: ymaoent@njmu.edu.cn.

PMID: 35605813
DOI: 10.1016/j.phrs.2022.106269

Abstract

Background: Siglec-15 (S15) is a type-I transmembrane protein and is considered a new candidate of immune checkpoint inhibitor for cancer immunotherapy.

Methods: In the present study, we first constructed and characterized a chimeric S15-specific monoclonal antibody (S15-4E6A). Then, the antitumor effectiveness and modulatory role of S15-4E6A in macrophages (mφs) were explored in vitro and in vivo. Finally, the underlying mechanism by which S15mAb inhibits LUAD was preliminarily explored.

Results: The results demonstrated the successful construction of S15-4E6A, and S15-4E6A exerted an efficacious tumor-inhibitory effect on LUAD cells and xenografts. S15-4E6A could promote M1-mφ polarization while inhibiting M2-mφ polarization, both in vitro and in vivo.

Conclusions: S15-based immunotherapy that functions by modulating mφ polarization may be a promising strategy for the treatment of S15-positive LUAD.

Keywords: Checkpoint inhibitor; Lung adenocarcinoma; Macrophage; Tumor microenvironment; siglec-15.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antibodies / pharmacology
Humans
Immunotherapy
Macrophages* / metabolism
Neoplasms* / metabolism
Sialic Acid Binding Immunoglobulin-like Lectins / metabolism
Sialic Acid Binding Immunoglobulin-like Lectins / pharmacology
Tumor Microenvironment

Substances

Antibodies
Sialic Acid Binding Immunoglobulin-like Lectins