Although chimeric antigen receptor-modified(CAR)T cell therapy has been successfully applied in the treatment of acute B lymphocytic leukemia,its effect on Burkitt lymphoma(BL)and chronic B lymphocytic leukemia(B-CLL)...Although chimeric antigen receptor-modified(CAR)T cell therapy has been successfully applied in the treatment of acute B lymphocytic leukemia,its effect on Burkitt lymphoma(BL)and chronic B lymphocytic leukemia(B-CLL)is unsatisfactory.Moreover,fatal side effects greatly impede CAR T cell application.Extracellular vesicles(EVs)are excellent carriers of therapeutic agents.Nevertheless,EVs mainly accumulate in the liver when administered without modification.As an envelope glycoprotein of Epstein–Barr viruses,gp350 can efficiently bind CD21 on B cells.Here,gp350 was directly anchored onto red blood cell EVs(RBC-EVs)via its transmembrane region combined with low-voltage electroporation.The results showed that gp350 could anchor to RBC-EVs with high efficiency and that the resulting gp350-anchored RBC-EVs(RBC-EVs/gp350^(Etp))exhibited increased targeting to CD21+BL and B-CLL relative to RBC-EVs.After the loading of doxorubicin or fludarabine,RBC-EVs/gp350^(Etp) had powerful cytotoxicity and therapeutic efficacy on CD21+BL or B-CLL,respectively.Moreover,RBC-EVs/gp350^(Etp) loaded with a drug did not exhibit any apparent systemic toxicity and specifically induced the apoptosis of tumor B cells but not normal Bcells.Therefore,our findings indicate that drug-loaded RBC-EVs/gp350^(Etp) may be adopted in the treatment of CD21+B cell malignancies.展开更多
B cell malignancies pose challenges due to therapeutic resistance and repeated relapse.Advances in adoptive cellular therapies including chimeric antigen receptor(CAR)-T cells have the potential to transform the treat...B cell malignancies pose challenges due to therapeutic resistance and repeated relapse.Advances in adoptive cellular therapies including chimeric antigen receptor(CAR)-T cells have the potential to transform the treat-ment landscape in hematological and solid tumor cancers.Improvements in constructs of CAR-T have improved specificity in targeting malignant cells.Multiple clinical trials have demonstrated the efficacy of CAR-T and other cellular treatments.In spite of advances in cellular therapies,hurdles in managing toxicities and lingering resis-tance remain.This review aims to summarize current innovations in adoptive cellular therapies and introduces future paths of discovery that will enhance these therapies in the era of precision oncology.展开更多
基金supported by the Natural Science Foundation of Zhejiang Province(LY19H160009 and LY20H120007)the National Natural Science Foundation of China(82130053,81971871,31970845 and 81901571)+1 种基金the Joint Preresearch Fund for Clinical Scientific Research of Hangzhou First People’s Hospital Affiliated to Zhejiang University(YYJJ2019Z07)the Major Project of Hangzhou Health Science and Technology Plan(Z20200134).
文摘Although chimeric antigen receptor-modified(CAR)T cell therapy has been successfully applied in the treatment of acute B lymphocytic leukemia,its effect on Burkitt lymphoma(BL)and chronic B lymphocytic leukemia(B-CLL)is unsatisfactory.Moreover,fatal side effects greatly impede CAR T cell application.Extracellular vesicles(EVs)are excellent carriers of therapeutic agents.Nevertheless,EVs mainly accumulate in the liver when administered without modification.As an envelope glycoprotein of Epstein–Barr viruses,gp350 can efficiently bind CD21 on B cells.Here,gp350 was directly anchored onto red blood cell EVs(RBC-EVs)via its transmembrane region combined with low-voltage electroporation.The results showed that gp350 could anchor to RBC-EVs with high efficiency and that the resulting gp350-anchored RBC-EVs(RBC-EVs/gp350^(Etp))exhibited increased targeting to CD21+BL and B-CLL relative to RBC-EVs.After the loading of doxorubicin or fludarabine,RBC-EVs/gp350^(Etp) had powerful cytotoxicity and therapeutic efficacy on CD21+BL or B-CLL,respectively.Moreover,RBC-EVs/gp350^(Etp) loaded with a drug did not exhibit any apparent systemic toxicity and specifically induced the apoptosis of tumor B cells but not normal Bcells.Therefore,our findings indicate that drug-loaded RBC-EVs/gp350^(Etp) may be adopted in the treatment of CD21+B cell malignancies.
文摘B cell malignancies pose challenges due to therapeutic resistance and repeated relapse.Advances in adoptive cellular therapies including chimeric antigen receptor(CAR)-T cells have the potential to transform the treat-ment landscape in hematological and solid tumor cancers.Improvements in constructs of CAR-T have improved specificity in targeting malignant cells.Multiple clinical trials have demonstrated the efficacy of CAR-T and other cellular treatments.In spite of advances in cellular therapies,hurdles in managing toxicities and lingering resis-tance remain.This review aims to summarize current innovations in adoptive cellular therapies and introduces future paths of discovery that will enhance these therapies in the era of precision oncology.
