摘要
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.
基金
The National Major Scientific and Technological Special Project for“Significant New Drugs Development,”No.SQ2018ZX090201
The Strategic Priority Research Program of the Chinese Academy of Sciences,Grant No.XDB19030205,No.XDA12050305
Guangdong Provincial Applied Science and Technology Research&Development Program,No.2016B020237006
Guangdong Special Support Program,NO.2017TX04R102
Frontier and key technology innovation special grant from the Department of Science and Technology of Guangdong province,No.2015B020227003
Natural Science Fund of Guangdong Province:Distinguished Young Scholars(Grant No.:2014A030306028)
Doctoral Foundation,No.:2017A030310381
National Natural Science Foundation of China(NSFC),No.81773301,81700156,81870121,81873847
Frontier Research Program of Guangzhou Regenerative Medicine and Health Guangdong Laboratory,No.2018GZR110105003
Science and Technology Planning Project of Guangdong Province,China(2017B030314056)
Guangzhou Medical University High-level University Construction Research Startup Fund,NO.B195002004013
Research Program of Hefei Institute of Stem Cell and Regenerative Medicine,No.2019YF001
Guangzhou science and technology plan project,NO.201907010042,201904010473.