Therapeutic antibodies targeting G protein-coupled receptors

Qingyuan Xu; Keke Huang; Yibing Shi; Yuanlin Song; Tianlei Ying; Zhenlin Yang

doi:10.1016/j.tips.2025.12.004

Therapeutic antibodies targeting G protein-coupled receptors

Trends Pharmacol Sci. 2026 Jan 7:S0165-6147(25)00284-6. doi: 10.1016/j.tips.2025.12.004. Online ahead of print.

Authors

Qingyuan Xu¹, Keke Huang², Yibing Shi³, Yuanlin Song⁴, Tianlei Ying⁵, Zhenlin Yang⁶

Affiliations

¹ Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai 200032, China; Shanghai Key Laboratory of Lung Inflammation and Injury, Shanghai 200032, China.
² Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.
³ Shanghai Institute of Infectious Disease and Biosecurity, Shanghai 200032, China.
⁴ Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai 200032, China; Shanghai Key Laboratory of Lung Inflammation and Injury, Shanghai 200032, China. Electronic address: song.yuanlin@zs-hospital.sh.cn.
⁵ Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai 200032, China; Shanghai Key Laboratory of Lung Inflammation and Injury, Shanghai 200032, China; Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Sciences, Fudan University, Shanghai 200032, China; Shanghai Institute of Infectious Disease and Biosecurity, Shanghai 200032, China; Shanghai Engineering Research Center for Synthetic Immunology, Shanghai 200032, China. Electronic address: tlying@fudan.edu.cn.
⁶ Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai 200032, China; Shanghai Key Laboratory of Lung Inflammation and Injury, Shanghai 200032, China; Shanghai Engineering Research Center for Synthetic Immunology, Shanghai 200032, China. Electronic address: yang_zhenlin@fudan.edu.cn.

PMID: 41507000
DOI: 10.1016/j.tips.2025.12.004

Abstract

G protein-coupled receptors (GPCRs) constitute the largest family of membrane proteins and are involved in numerous physiological and pathological processes. Therapeutic antibodies targeting GPCRs, including monoclonal antibodies (mAbs), single-domain antibodies (sdAbs), and antibody-drug conjugates (ADCs), represent a promising class of biologics with high specificity and therapeutic potential. The integration of innovative screening technologies, structural biology, and computational approaches has significantly accelerated the discovery of antibody-based therapeutics against GPCRs. In this review, we discuss the emerging strategies used in the development of these therapeutic antibodies, examine key insights from pathogenic autoantibodies, evaluate the clinical trial landscape, and explore how emerging technologies such as artificial intelligence (AI)-assisted design and membrane-mimetic systems are driving the next generation of GPCR-targeted therapeutics.

Keywords: GPCRs; antibody–drug conjugates; clinical trials; screening strategies; single-domain antibodies; therapeutic antibodies.

Publication types

Review