Development of NK cell-based cancer immunotherapies through receptor engineering  

作　　者：Audrey Page Nicolas Chuvin Jenny Valladeau-Guilemond Stéphane Depil 

机构地区：[1]Centre de Recherche en Cancérologie de Lyon,UMR INSERM U1052 CNRS 5286,Centre Léon Bérard,Lyon,France [2]ErVimmune,Lyon,France [3]Centre Léon Bérard,Lyon,France [4]UniversitéClaude Bernard Lyon 1,Lyon,France

出　　处：《Cellular & Molecular Immunology》2024年第4期315-331,共17页中国免疫学杂志（英文版）

基　　金：The AP postdoctoral position is funded by INCa PLBio 2020-095.

摘　　要：Natural killer(NK)cell-based immunotherapies are attracting increasing interest in the field of cancer treatment.Early clinical trials have shown promising outcomes,alongside satisfactory product efficacy and safety.Recent developments have greatly increased the therapeutic potential of NK cells by endowing them with enhanced recognition and cytotoxic capacities.This review focuses on surface receptor engineering in NK cell therapy and discusses its impact,challenges,and future directions.Most approaches are based on engineering with chimeric antigen receptors to allow NK cells to target specific tumor antigens independent of human leukocyte antigen restriction.This approach has increased the precision and potency of NK-mediated recognition and elimination of cancer cells.In addition,engineering NK cells with T-cell receptors also mediates the recognition of intracellular epitopes,which broadens the range of target peptides.Indirect tumor peptide recognition by NK cells has also been improved by optimizing immunoglobulin constant fragment receptor expression and signaling.Indeed,engineered NK cells have an improved ability to recognize and destroy target cells coated with specific antibodies,thereby increasing their antibodydependent cellular cytotoxicity.The ability of NK cell receptor engineering to promote the expansion,persistence,and infiltration of transferred cells in the tumor microenvironment has also been explored.Receptor-based strategies for sustained NK cell functionality within the tumor environment have also been discussed,and these strategies providing perspectives to counteract tumor-induced immunosuppression.Overall,receptor engineering has led to significant advances in NK cell-based cancer immunotherapies.As technical challenges are addressed,these innovative treatments will likely reshape cancer immunotherapy.

关 键 词：NK cells Cell therapy Receptor engineering CAR 

分 类 号：R730.51[医药卫生—肿瘤]