T-cell immunotherapy has progressed rapidly,evolving from native T-cell receptor biology to the development of innovative synthetic receptors that extend therapeutic applications beyond cancer.This review explores eng...T-cell immunotherapy has progressed rapidly,evolving from native T-cell receptor biology to the development of innovative synthetic receptors that extend therapeutic applications beyond cancer.This review explores engineering strategies,ranging from natural TCRs to synthetic receptors,that increase T-cell activation and therapeutic potential.We begin by highlighting the foundational role of native receptors in the T-cell response,emphasizing how these structural and functional insights inform the design of next-generation synthetic receptors.Comparisons between CAR and TCR-like synthetic receptors underscore their respective advantages in specificity,efficacy,and safety,as well as potential areas for further improvement.In addition,gene editing technologies such as CRISPR-Cas9 enable precise modifications to the T-cell genome,enhancing receptor performance and minimizing immunogenic risks.In addition to tumors,these engineered T cells can be directed against viral infections,autoimmune disorders,and other diseases.We also explore advanced strategies that engage multiple immune cell types to achieve synergistic,durable responses.By demonstrating how native and synthetic receptors collectively drive innovation,this review aims to inspire new research directions and ultimately expand the scope of T-cell engineering for universal therapeutic applications.展开更多
The need for novel therapeutics against human cancers such as leukemias and solid tumors is well recognized.Human T cells are poised to make a fundamental change in the therapeutic approach.T-cell interaction with a t...The need for novel therapeutics against human cancers such as leukemias and solid tumors is well recognized.Human T cells are poised to make a fundamental change in the therapeutic approach.T-cell interaction with a tumor cell is a critical event and primarily driven by T-cell receptor(TCR)recognition of peptide in the pocket HLA.However,among TCR-based T-cell therapies,either TCR mismatching or the low density of major histocompatibility complex causes tumor cells to escape from the immune response.TCR molecules have low binding affinities,preventing their recognitions.Undoubtedly,antibody therapeutics is an effective treatment for cancer.As the new generation of monoclonal antibodies,TCR-like antibodies can mimic TCR recognition but are not susceptible for mechanisms of tumor evasion from the immune response.As chimeric antigen receptor(CAR)structure expressed on the surface of T cells,TCR-like antibodies can confer antigen specificity to T cells.The new TCR-like CAR may be important to drive new technologies of adoptive cell therapy,in particular,T-cell therapy,and open possibilities to target endogenous tumor-specific antigens.展开更多
文摘T-cell immunotherapy has progressed rapidly,evolving from native T-cell receptor biology to the development of innovative synthetic receptors that extend therapeutic applications beyond cancer.This review explores engineering strategies,ranging from natural TCRs to synthetic receptors,that increase T-cell activation and therapeutic potential.We begin by highlighting the foundational role of native receptors in the T-cell response,emphasizing how these structural and functional insights inform the design of next-generation synthetic receptors.Comparisons between CAR and TCR-like synthetic receptors underscore their respective advantages in specificity,efficacy,and safety,as well as potential areas for further improvement.In addition,gene editing technologies such as CRISPR-Cas9 enable precise modifications to the T-cell genome,enhancing receptor performance and minimizing immunogenic risks.In addition to tumors,these engineered T cells can be directed against viral infections,autoimmune disorders,and other diseases.We also explore advanced strategies that engage multiple immune cell types to achieve synergistic,durable responses.By demonstrating how native and synthetic receptors collectively drive innovation,this review aims to inspire new research directions and ultimately expand the scope of T-cell engineering for universal therapeutic applications.
基金support from the Science and Technology Development Fund,Macao SAR(File No.FDCT/131/2016/A3,FDCT/0015/2018/A1)the Guangzhou Science and Technology Program(201807010004)+2 种基金the Multi-Year Research Grant(File No.MYRG2019-00069-FHS)Start-up Research Grand(File No.SRG2016-00082-FHS)the intramural research program of Faculty of Health Sciences,University of Macao.
文摘The need for novel therapeutics against human cancers such as leukemias and solid tumors is well recognized.Human T cells are poised to make a fundamental change in the therapeutic approach.T-cell interaction with a tumor cell is a critical event and primarily driven by T-cell receptor(TCR)recognition of peptide in the pocket HLA.However,among TCR-based T-cell therapies,either TCR mismatching or the low density of major histocompatibility complex causes tumor cells to escape from the immune response.TCR molecules have low binding affinities,preventing their recognitions.Undoubtedly,antibody therapeutics is an effective treatment for cancer.As the new generation of monoclonal antibodies,TCR-like antibodies can mimic TCR recognition but are not susceptible for mechanisms of tumor evasion from the immune response.As chimeric antigen receptor(CAR)structure expressed on the surface of T cells,TCR-like antibodies can confer antigen specificity to T cells.The new TCR-like CAR may be important to drive new technologies of adoptive cell therapy,in particular,T-cell therapy,and open possibilities to target endogenous tumor-specific antigens.
