CD19 chimeric antigen receptor(CAR)T cells have shown robust efficacy in relapsed and refractory acute lymphoblastic leukemia(R/R ALL),but compromising result in chronic lymphoblastic leukemia(CLL)and non-Hodgkin’s l...CD19 chimeric antigen receptor(CAR)T cells have shown robust efficacy in relapsed and refractory acute lymphoblastic leukemia(R/R ALL),but compromising result in chronic lymphoblastic leukemia(CLL)and non-Hodgkin’s lymphoma(NHL).CD19-relapse and the lack of CAR-T cell persistence which result in treatment failure are considerable obstacles to overcome.CAR-T targeting CD20 is an option for salvaging CD19 CAR-T failure.Previous studies have established variant structures of bispecific CAR-T which could avoid antigen-loss and immune escape.Here,we constructed tandem and loop CAR structures targeting both CD19 and CD20 antigen.Bispecific CAR-T cells could eliminate either CD19 or CD20 negative lymphoma cells,suggesting they exhibited dual antigen targeting of CD19 and CD20.By comparing the efficiency of four bispecific CAR modified T cells,it was found that loop2019 CAR was the best structure among them to eradicate lymphoma cell lines and patients’primary lymphoma or CLL cells in a very low dose in vitro and prolong the survival time dramatically in lymphoma xenograft mice model.These data highlighted the potential of loop2019 CAR-T in clinical treatment.展开更多
Dear Editor,Antigen escape is responsible for resistance[1]or disease relapse[2]from single-target chimeric antigen receptor(CAR)-T therapy.Dual-target CAR-T therapy has the potential to overcome the escape problem.Ho...Dear Editor,Antigen escape is responsible for resistance[1]or disease relapse[2]from single-target chimeric antigen receptor(CAR)-T therapy.Dual-target CAR-T therapy has the potential to overcome the escape problem.However,the efficacy and safety assessment of dual-target CAR-T therapy in treating acute myeloid leukemia(AML)need further investigation.Tandem CAR-T therapy has been widely used in research and clinic.However,clustering of two connected single-chain variable fragments(scFvs)[3]and the inappropriate conjugation distance[4]pose a risk of damaging tandem CAR-T cells’function.展开更多
基金supported by the National Key Research&Development Program of China(2019YFA0110200)the National Natural Science Foundation of China(81830005)+1 种基金the CAMS Innovation Fund for Medical Sciences(2021-I2M-1-041)the Tianjin Applied Fundamental Research Planning Key Project(20JCZDJC00120)。
文摘CD19 chimeric antigen receptor(CAR)T cells have shown robust efficacy in relapsed and refractory acute lymphoblastic leukemia(R/R ALL),but compromising result in chronic lymphoblastic leukemia(CLL)and non-Hodgkin’s lymphoma(NHL).CD19-relapse and the lack of CAR-T cell persistence which result in treatment failure are considerable obstacles to overcome.CAR-T targeting CD20 is an option for salvaging CD19 CAR-T failure.Previous studies have established variant structures of bispecific CAR-T which could avoid antigen-loss and immune escape.Here,we constructed tandem and loop CAR structures targeting both CD19 and CD20 antigen.Bispecific CAR-T cells could eliminate either CD19 or CD20 negative lymphoma cells,suggesting they exhibited dual antigen targeting of CD19 and CD20.By comparing the efficiency of four bispecific CAR modified T cells,it was found that loop2019 CAR was the best structure among them to eradicate lymphoma cell lines and patients’primary lymphoma or CLL cells in a very low dose in vitro and prolong the survival time dramatically in lymphoma xenograft mice model.These data highlighted the potential of loop2019 CAR-T in clinical treatment.
基金supported by the National Key Research and Development Program of China(2021YFC2500300)the National Natural Science Foundation of China(81830005)+1 种基金Haihe Laboratory of Cell Ecosystem Innova-tion Fund(HH22KYZX0032)the Chinese Academy of Medical Sciences(CAMS)Innovation Fund for Medical Sciences(2020-I2M-C&T-A-019).
文摘Dear Editor,Antigen escape is responsible for resistance[1]or disease relapse[2]from single-target chimeric antigen receptor(CAR)-T therapy.Dual-target CAR-T therapy has the potential to overcome the escape problem.However,the efficacy and safety assessment of dual-target CAR-T therapy in treating acute myeloid leukemia(AML)need further investigation.Tandem CAR-T therapy has been widely used in research and clinic.However,clustering of two connected single-chain variable fragments(scFvs)[3]and the inappropriate conjugation distance[4]pose a risk of damaging tandem CAR-T cells’function.
