Although chimeric antigen receptor T-cell(CAR-T-cell)therapy has shown excellent efficacy against refractory/relapsed B-cell lymphoma,B-cell acute lymphoblastic leukemia and multiple myeloma,1,2 the complete response ...Although chimeric antigen receptor T-cell(CAR-T-cell)therapy has shown excellent efficacy against refractory/relapsed B-cell lymphoma,B-cell acute lymphoblastic leukemia and multiple myeloma,1,2 the complete response rate of patients with refractory/relapsed B-cell lymphoma receiving conventional CAR-T-cell therapy is approximately 40%to 50%.3–5 There are 3 drawbacks to viral CAR-T-cell therapy.First,random integration of the CAR cassette and lentivirus replication are potential risks for viral CAR-T-cell therapy(Fig.1A).展开更多
Chimeric antigen receptor T(CAR-T)cells have emerged as novel and promising immune therapies for the treatment of multiple types of cancer in patients with hematological malignancies.There are several key components c...Chimeric antigen receptor T(CAR-T)cells have emerged as novel and promising immune therapies for the treatment of multiple types of cancer in patients with hematological malignancies.There are several key components critical for development and application of CAR-T therapy.First,the design of CAR vectors can considerably affect several aspects of the physiological functions of these T cells.Moreover,despite the wide use of g-retrovirus and lentivirus in mediating gene transfer into T cells,optimal CAR delivery systems are also being developed and evaluated.In addition,several classes of mouse models have been used to evaluate the efficacies of CART cells;however,each model has its own limitations.Clinically,although surprising complete remission(CR)rates were observed in acute lymphoblastic leukemia(ALL),lymphoma,and multiple myeloma(MM),there is still a lack of specific targets for acute myeloid leukemia(AML).Leukemia relapse remains a major challenge,and its mechanism is presently under investigation.Cytokine release syndrome(CRS)and neurotoxicity are life-threatening adverse effects that need to be carefully treated.Several factors that compromise the activities of anti-solid cancer CAR-T cells have been recognized,and further improvements targeting these factors are the focus of the development of novel CAR-T cells.Overcoming the current hurdles will lead to optimal responses of CAR-T cells,thus paving the way for their wide clinical application.展开更多
文摘Although chimeric antigen receptor T-cell(CAR-T-cell)therapy has shown excellent efficacy against refractory/relapsed B-cell lymphoma,B-cell acute lymphoblastic leukemia and multiple myeloma,1,2 the complete response rate of patients with refractory/relapsed B-cell lymphoma receiving conventional CAR-T-cell therapy is approximately 40%to 50%.3–5 There are 3 drawbacks to viral CAR-T-cell therapy.First,random integration of the CAR cassette and lentivirus replication are potential risks for viral CAR-T-cell therapy(Fig.1A).
基金The National Major Scientific and Technological Special Project for“Significant New Drugs Development,”No.SQ2018ZX090201The Strategic Priority Research Program of the Chinese Academy of Sciences,Grant No.XDB19030205,No.XDA12050305+10 种基金Guangdong Provincial Applied Science and Technology Research&Development Program,No.2016B020237006Guangdong Special Support Program,NO.2017TX04R102Frontier and key technology innovation special grant from the Department of Science and Technology of Guangdong province,No.2015B020227003Natural Science Fund of Guangdong Province:Distinguished Young Scholars(Grant No.:2014A030306028)Doctoral Foundation,No.:2017A030310381National Natural Science Foundation of China(NSFC),No.81773301,81700156,81870121,81873847Frontier Research Program of Guangzhou Regenerative Medicine and Health Guangdong Laboratory,No.2018GZR110105003Science and Technology Planning Project of Guangdong Province,China(2017B030314056)Guangzhou Medical University High-level University Construction Research Startup Fund,NO.B195002004013Research Program of Hefei Institute of Stem Cell and Regenerative Medicine,No.2019YF001Guangzhou science and technology plan project,NO.201907010042,201904010473.
文摘Chimeric antigen receptor T(CAR-T)cells have emerged as novel and promising immune therapies for the treatment of multiple types of cancer in patients with hematological malignancies.There are several key components critical for development and application of CAR-T therapy.First,the design of CAR vectors can considerably affect several aspects of the physiological functions of these T cells.Moreover,despite the wide use of g-retrovirus and lentivirus in mediating gene transfer into T cells,optimal CAR delivery systems are also being developed and evaluated.In addition,several classes of mouse models have been used to evaluate the efficacies of CART cells;however,each model has its own limitations.Clinically,although surprising complete remission(CR)rates were observed in acute lymphoblastic leukemia(ALL),lymphoma,and multiple myeloma(MM),there is still a lack of specific targets for acute myeloid leukemia(AML).Leukemia relapse remains a major challenge,and its mechanism is presently under investigation.Cytokine release syndrome(CRS)and neurotoxicity are life-threatening adverse effects that need to be carefully treated.Several factors that compromise the activities of anti-solid cancer CAR-T cells have been recognized,and further improvements targeting these factors are the focus of the development of novel CAR-T cells.Overcoming the current hurdles will lead to optimal responses of CAR-T cells,thus paving the way for their wide clinical application.
