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

Pharmacological Research (Jul 2022)

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

Affiliations

Xuejun Xiao: Department of Pharmacology, Xinjiang Medical University, Urumqi, China
Yan Peng: 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
Zheyue Wang: 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
Louqian Zhang: Department of Thoracic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China
Tingting Yang: 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
Yangyang Sun: Department of Pathology, Changzhou No. 2 People's Hospital Affiliated with Nanjing Medical University, Changzhou, China
Yufeng Chen: 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
Wenqing Zhang: 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
Xinxia Chang: 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
Wen Huang: Department of Oncology, The Fourth Affiliated Hospital of Nanjing Medical University, Nanjing, China
Shuning Tian: NHC Key Laboratory of Antibody Technique, Nanjing Medical University, Nanjing, China; Jiangsu Province Engineering Research Center of Antibody Drug, Nanjing Medical University, Nanjing, China
Zhenqing Feng: 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
Nabi Xinhua: Department of Pharmacology, Xinjiang Medical University, Urumqi, China; Corresponding author.
Qi Tang: 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; Corresponding author at: NHC Key Laboratory of Antibody Technique, Nanjing Medical University, Nanjing, China.
Yuan Mao: 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; Corresponding author at: Department of Oncology, The Fourth Affiliated Hospital of Nanjing Medical University, Nanjing, China.

Journal volume & issue: Vol. 181
p. 106269

Abstract

Read online

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.

Published in Pharmacological Research

ISSN: 1096-1186 (Online)
Publisher: Elsevier
Country of publisher: United Kingdom
LCC subjects: Medicine: Therapeutics. Pharmacology
Website: https://www.sciencedirect.com/journal/pharmacological-research

About the journal

Abstract

Keywords