首页|Development of pharmacological immunoregulatory anti-cancer therapeutics:current mechanistic studies and clinical opportunities

Development of pharmacological immunoregulatory anti-cancer therapeutics:current mechanistic studies and clinical opportunities

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Immunotherapy represented by anti-PD-(L)1 and anti-CTLA-4 inhibitors has revolutionized cancer treatment,but challenges related to resistance and toxicity still remain.Due to the advancement of immuno-oncology,an increasing number of novel immunoregulatory targets and mechanisms are being revealed,with relevant therapies promising to improve clinical immunotherapy in the foreseeable future.Therefore,comprehending the larger picture is important.in this review,we analyze and summarize the current landscape of preclinical and translational mechanistic research,drug development,and clinical trials that brought about next-generation pharmacological immunoregulatory anti-cancer agents and drug candidates beyond classical immune checkpoint inhibitors.Along with further clarification of cancer immunobiology and advances in antibody engineering,agents targeting additional inhibitory immune checkpoints,including LAG-3,TIM-3,TIGIT,CD47,and B7 family members are becoming an important part of cancer immunotherapy research and discovery,as are structurally and functionally optimized novel anti-PD-(L)1 and anti-CTLA-4 agents and agonists of co-stimulatory molecules of T cells.Exemplified by bispecific T cell engagers,newly emerging bi-specific and multi-specific antibodies targeting immunoregulatory molecules can provide considerable clinical benefits.Next-generation agents also include immune epigenetic drugs and cytokine-based therapeutics.Cell therapies,cancer vaccines,and oncolytic viruses are not covered in this review.This comprehensive review might aid in further development and the fastest possible clinical adoption of effective immuno-oncology modalities for the benefit of patients.

Nanhao Yin、Xintong Li、Xuanwei Zhang、Shaolong Xue、Yu Cao、Gabriele Niedermann、You Lu、Jianxin Xue

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Division of Thoracic Tumor Multimodality Treatment,Cancer Center & State Key Laboratory of Biotherapy,and The National Clinical Research Center for Geriatrics,West China Hospital,Sichuan University,No.37,Guoxue Lane,Chengdu 610041 Sichuan,PR China

Department of Gynecology and Obstetrics,West China Second University Hospital,Sichuan University,No.20,Section 3,South Renmin Road,Chengdu 610041 Sichuan,PR China

Department of Emergency Medicine,Laboratory of Emergency Medicine,West China Hospital,Sichuan University,No.37,Guoxue Lane,Chengdu 610041 Sichuan,PR China

Institute of Disaster Medicine & Institute of Emergency Medicine,Sichuan University,No.17,Gaopeng Avenue,Chengdu 610041 Sichuan,PR China

Department of Radiation Oncology,Medical Center-University of Freiburg,Faculty of Medicine,University of Freiburg,German Cancer Consortium(DKTK)Partner Site DKTK-Freiburg,Robert-Koch-Strasse 3,79106 Freiburg,Germany

Laboratory of Clinical Cell Therapy,West China Hospital,Sichuan University,No.2222,Xinchuan Road,Chengdu 610041 Sichuan,PR China

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1·3·5 project for disciplines of excellence,West China Hospital,Sichuan UniversityNational Natural Science Foundation of ChinaNational Clinical Research Center for GeriatricsSichuan Provincial Research FoundationOutstanding Youth Talent Foundation for Science and Technology of Sichuan Province

ZYJC2100382373021Z2021JC00124NSFSC68622022JDJQ0056

2024

10.1038/s41392-024-01826-z

信号转导与靶向治疗(英文)

信号转导与靶向治疗(英文)

CSTPCD
ISSN：
年,卷(期)：2024.9(6)