Chimeric antigen receptor(CAR)T cells have been indicated effective in treating B cell acute lymphoblastic leukemia and non-Hodgkin lymphoma and have shown encouraging results in preclinical and clinical studies.Howev...Chimeric antigen receptor(CAR)T cells have been indicated effective in treating B cell acute lymphoblastic leukemia and non-Hodgkin lymphoma and have shown encouraging results in preclinical and clinical studies.However,CAR T cells have achieved minimal success against solid malignancies because of the additional obstacles of their insufficient migration into tumors and poor amplification and persistence,in addition to antigen-negative relapse and an immunosuppressive microenvironment.Various preclinical studies are exploring strategies to overcome the above challenges.Mobilization of endogenous immune cells is also necessary for CAR T cells to obtain their optimal therapeutic effect given the importance of the innate immune responses in the elimination of malignant tumors.In this review,we focus on the recent advances in the engineering of CAR T cell therapies to restore the immune response in solid malignancies,especially with CAR T cells acting as cellular carriers to deliver immunomodulators to tumors to mobilize the endogenous immune response.We also explored the sensitizing effects of conventional treatment approaches,such as chemotherapy and radiotherapy,on CAR T cell therapy.Finally,we discuss the combination of CAR T cells with biomaterials or oncolytic viruses to enhance the anti-tumor outcomes of CAR T cell therapies in solid tumors.展开更多
Cytokine release syndrome(CRS)is a major obstacle to the widespread clinical application of chimeric antigen receptor(CAR)T cell therapies.CRS can also be induced by infections(such as SARS-CoV-2),drugs(such as therap...Cytokine release syndrome(CRS)is a major obstacle to the widespread clinical application of chimeric antigen receptor(CAR)T cell therapies.CRS can also be induced by infections(such as SARS-CoV-2),drugs(such as therapeutic antibodies),and some autoimmune diseases.Myeloid-derived macrophages play key roles in the pathogenesis of CRS,and participate in the production and release of the core CRS cytokines,including interleukin(IL)-1,IL-6,and interferon-γ.In this review,we summarize the roles of macrophages in CRS and discuss new developments in macrophage activation and the related mechanisms of cytokine regulation in CRS.展开更多
Chimeric antigen receptor(CAR)T-cell therapy is an effective new treatment strategy for hematologic malignancies.The success of CAR T-cell therapy in treating leukemia and lymphoma has promoted its development for mul...Chimeric antigen receptor(CAR)T-cell therapy is an effective new treatment strategy for hematologic malignancies.The success of CAR T-cell therapy in treating leukemia and lymphoma has promoted its development for multiple myeloma(MM),and the initial results of CAR T cell therapy have been encouraging.CAR T-cell therapy target antigens that have been clinically evaluated in MM;these antigens include CD19,B cell maturation antigen(BCMA),CD38,and CD138.A barrier to the widespread use of CAR T-cell therapy is its toxicity,primarily cytokine release syndrome(CRS),and neurologic toxicity.This study reports a patient with refractory MM who also developed megakaryocyte aplastic thrombocytopenia after receiving CAR T-cell therapy;such a case or the unusual side effects involving medications are yet unreported.There are risks in using cyclosporine and other immunosuppressants that may lead to MM recurrence as the use of such substances is contradictory to previous treatments;therefore,we temporarily administered platelet infusion as supportive care.Thus far,the condition of the patient has been steady and the patient regularly takes blood test in the hospital.展开更多
The treatment of gastrointestinal cancer has always been a crucial research area,and targeted therapy has been receiving increasing attention.At present,the effect of targeted therapy is unsatisfactory for gastric can...The treatment of gastrointestinal cancer has always been a crucial research area,and targeted therapy has been receiving increasing attention.At present,the effect of targeted therapy is unsatisfactory for gastric cancer.Thus,the discovery of new targets is crucial.Claudin 18.2(CLDN18.2),a member of the claudin family,belongs to the tight junction protein family that controls the flow of molecules between cell layers.CLDN18.2 expression has been discussed in many studies.In recent years,there have been many studies on targeted therapy with CLDN18.2-ideal monoclonal antibody 362.Furthermore,CLDN18.2-specific chimeric antigen receptor T therapy has been used for CLDN18.2-positive tumors,such as gastric and pancreatic cancers.Considerable research has been focused on CLDN18.2.CLDN18.2,a newly discovered marker for precise targeted therapy of gastric cancer,could offer new hope for the treatment of gastric cancer.展开更多
The current standard of care in hematological malignancies has brought considerable clinical benefits to patients.However,important bottlenecks still limit optimal achievements following a current medical practice.The...The current standard of care in hematological malignancies has brought considerable clinical benefits to patients.However,important bottlenecks still limit optimal achievements following a current medical practice.The genetic complexity of the diseases and the heterogeneity of tumor clones cause difficulty in ensuring long-term efficacy of conventional treatments for most hematological disorders.Consequently,new treatment strategies are necessary to improve clinical outcomes.Chimeric antigen receptor T-cell(CAR T)immunotherapy opens a new path for targeted therapy of hematological malignancies.In this review,through a representative case study,we summarize the current experience of CAR T-cell therapy,the management of common side effects,the causative mechanisms of therapy resistance,and new strategies to improve the efficacy of CAR T-cell therapy.展开更多
Although antiretroviral therapy(ART)can reduce the viral load in the plasma to undetectable levels in human immunodeficiency virus(HIV)-infected individuals,ART alone cannot completely eliminate HIV due to its integra...Although antiretroviral therapy(ART)can reduce the viral load in the plasma to undetectable levels in human immunodeficiency virus(HIV)-infected individuals,ART alone cannot completely eliminate HIV due to its integration into the host cell genome to form viral reservoirs.To achieve a functional cure for HIV infection,numerous preclinical and clinical studies are underway to develop innovative immunotherapies to eliminate HIV reservoirs in the absence of ART.Early studies have tested adoptive T-cell therapies in HIV-infected individuals,but their effectiveness was limited.In recent years,with the technological progress and great success of chimeric antigen receptor(CAR)therapy in the treatment of hematological malignancies,CAR therapy has gradually shown its advantages in the field of HIV infection.Many studies have identified a variety of HIV-specific CAR structures and types of cytolytic effector cells.Therefore,CAR therapy may be beneficial for enhancing HIV immunity,achieving HIV control,and eliminating HIV reservoirs,gradually becoming a promising strategy for achieving a functional HIV cure.In this review,we provide an overview of the design of anti-HIV CAR proteins,the cell types of anti-HIV CAR(including CAR T cells,CAR natural killer cells,and CAR-encoding hematopoietic stem/progenitor cells),the clinical application of CAR therapy in HIV infection,and the prospects and challenges in anti-HIV CAR therapy for maintaining viral suppression and eliminating HIV reservoirs.展开更多
The ability to control mammalian cells such that they self-organize or enact therapeutic effects as desired has incredible implications.Not only would it further our understanding of native processes such as developme...The ability to control mammalian cells such that they self-organize or enact therapeutic effects as desired has incredible implications.Not only would it further our understanding of native processes such as development and the immune response,but it would also have powerful applications in medical fields such as regenerative medicine and immunotherapy.This control is typically obtained by synthetic circuits that use synthetic receptors,but control remains incomplete.The synthetic juxtacrine receptors(SJRs)are widely used as they are fully modular and enable spatial control,but they have limited gene expression amplification and temporal control.As these are integral facets to cell control,I therefore designed transcription factor based amplifiers that amplify gene expression and enable unidirectional temporal control by prolonging duration of target gene expression.Using a validated in silico framework for SJR signaling,I combined these amplifiers with SJRs and show that these SJR amplifier circuits can direct spatiotemporal patterning and improve the quality of self-organization.I then show that these circuits can improve chimeric antigen receptor(CAR)T cell tumor killing against various heterogenous antigen expression tumors.These amplifiers are flexible tools that improve control over SJR based circuits with both basic and therapeutic applications.展开更多
Malignant mesothelioma(MM)is a rare,aggressive solid tumor with limited therapeutic options and poor therapeutic response.The role of immunotherapy in MM is now well established and therapeutic options,such as checkpo...Malignant mesothelioma(MM)is a rare,aggressive solid tumor with limited therapeutic options and poor therapeutic response.The role of immunotherapy in MM is now well established and therapeutic options,such as checkpoint inhibitors,are increasingly being approved.Chimeric antigen receptor(CAR)-T cell therapy is successfully implemented in several hematologic cancers,but currently has inadequate effect in solid tumors,owing to several limitations,such as trafficking and infiltration,limited T cell persistence and exhaustion,the immunosuppressive TME and tumor antigen heterogeneity.The lack of uniform and universal expression of tumor-associated antigens(TAAs)on tumor cells,as well as TAA heterogeneity following tumor editing post-therapy,are issues of significant importance to CAR-T cell and associated antigen-targeting therapies.Our review discusses the concept of tumor antigen heterogeneity in MM,the consequences for CAR-T cell therapies and the strategies to overcome it.展开更多
Chimeric antigen receptor(CAR)T cell therapy is a relatively new form of targeted therapy that has demonstrated impressive success in treating hematological malignancies.It has been challenging to translate this succe...Chimeric antigen receptor(CAR)T cell therapy is a relatively new form of targeted therapy that has demonstrated impressive success in treating hematological malignancies.It has been challenging to translate this success to solid tumors.Reasons for this include barriers to delivery,tumor heterogeneity,cancer cells'ability to evade the immune system as well as identifying the optimal target.Most CAR T clinical trials have targeted well‐characterized cancer targets with significant preclinical and in some cases clinical validation.Published results from some of these trials show signs of anti‐cancer activity that warrant encouragement,but also caution,given instances of unacceptable toxicity.The narrow therapeutic window is complicated by the ability of CAR T cells to expand in patients regardless of dose.Here,we review those trials showing encouraging results in the context of target selection.It is clear that more specific tumor targeting is required,either by affinity tuning to avoid low‐level target expression in healthy cells,logic gating,or the identification of new targets that are more cancer specific.展开更多
The immune system is a fascinating world of cells,soluble factors,interacting cells,and tissues,all of which are interconnected.The highly complex nature of the immune system makes it difficult to view it as a whole,b...The immune system is a fascinating world of cells,soluble factors,interacting cells,and tissues,all of which are interconnected.The highly complex nature of the immune system makes it difficult to view it as a whole,but researchers are now trying to put all the pieces of the puzzle together to obtain a more complete picture.The development of new specialized equipment and immunological techniques,genetic approaches,animal models,and a long list of monoclonal antibodies,among many other factors,are improving our knowledge of this sophisticated system.The different types of cell subsets,soluble factors,membrane molecules,and cell functionalities are some aspects that we are starting to understand,together with their roles in health,aging,and illness.This knowledge is filling many of the gaps,and in some cases,it has led to changes in our previous assumptions;e.g.,adaptive immune cells were previously thought to be unique memory cells until trained innate immunity was observed,and several innate immune cells with features similar to those of cytokine-secreting T cells have been discovered.Moreover,we have improved our knowledge not only regarding immune-mediated illnesses and how the immune system works and interacts with other systems and components(such as the microbiome)but also in terms of ways to manipulate this system through immunotherapy.The development of different types of immunotherapies,including vaccines(prophylactic and therapeutic),and the use of pathogens,m onodonal antibodies,recombinant proteins,cytokines,and cellular immunotherapies,are changing the way in which we approach many diseases,especially cancer.展开更多
Multiple myeloma(MM),considered an incurable hematological malignancy,is characterized by its clonal evolution of malignant plasma cells.Although the application of autologous stem cell transplantation(ASCT)and the in...Multiple myeloma(MM),considered an incurable hematological malignancy,is characterized by its clonal evolution of malignant plasma cells.Although the application of autologous stem cell transplantation(ASCT)and the introduction of novel agents such as immunomodulatory drugs(IMiDs)and proteasome inhibitors(PIs)have doubled the median overall survival to eight years,relapsed and refractory diseases are still frequent events in the course of MM.To achieve a durable and deep remission,immunotherapy modalities have been developed for relapsed/refractory multiple myeloma(RRMM).Among these approaches,chimeric antigen receptor(CAR)T-cell therapy is the most promising star,based on the results of previous success in B-cell neoplasms.In this immunotherapy,autologous T cells are engineered to express an artificial receptor which targets a tumor-associated antigen and initiates the T-cell killing procedure.Tisagenlecleucel and Axicabtagene,targeting the CD19 antigen,are the two pacesetters of CAR T-cell products.They were approved by the US Food and Drug Administration(FDA)in 2017 for the treatment of acute lymphocytic leukemia(ALL)and diffuse large B-cell lymphoma(DLBCL).Their development enabled unparalleled efficacy in combating hematopoietic neoplasms.In this review article,we summarize six promising candidate antigens in MM that can be targeted by CARs and discuss some noteworthy studies of the safety profile of current CAR T-cell therapy.展开更多
基金This work was supported by the National Natural Science Foundation of China(Nos.31991171,81830002,and 31540016)National Key R&D Program of China(No.2018 YFC1313400).
文摘Chimeric antigen receptor(CAR)T cells have been indicated effective in treating B cell acute lymphoblastic leukemia and non-Hodgkin lymphoma and have shown encouraging results in preclinical and clinical studies.However,CAR T cells have achieved minimal success against solid malignancies because of the additional obstacles of their insufficient migration into tumors and poor amplification and persistence,in addition to antigen-negative relapse and an immunosuppressive microenvironment.Various preclinical studies are exploring strategies to overcome the above challenges.Mobilization of endogenous immune cells is also necessary for CAR T cells to obtain their optimal therapeutic effect given the importance of the innate immune responses in the elimination of malignant tumors.In this review,we focus on the recent advances in the engineering of CAR T cell therapies to restore the immune response in solid malignancies,especially with CAR T cells acting as cellular carriers to deliver immunomodulators to tumors to mobilize the endogenous immune response.We also explored the sensitizing effects of conventional treatment approaches,such as chemotherapy and radiotherapy,on CAR T cell therapy.Finally,we discuss the combination of CAR T cells with biomaterials or oncolytic viruses to enhance the anti-tumor outcomes of CAR T cell therapies in solid tumors.
基金supported by grants from the National Key Research and Development Program of China(Grant No.2020YFA0707704)the National Key Research and Development Program of China(Grant No.2016YFC1303800)+1 种基金the Jilin Scientific and Technological Development Program(CN)(Grant No.20190303146SF)the National Natural Science Foundation of China(Grant No.81874052).
文摘Cytokine release syndrome(CRS)is a major obstacle to the widespread clinical application of chimeric antigen receptor(CAR)T cell therapies.CRS can also be induced by infections(such as SARS-CoV-2),drugs(such as therapeutic antibodies),and some autoimmune diseases.Myeloid-derived macrophages play key roles in the pathogenesis of CRS,and participate in the production and release of the core CRS cytokines,including interleukin(IL)-1,IL-6,and interferon-γ.In this review,we summarize the roles of macrophages in CRS and discuss new developments in macrophage activation and the related mechanisms of cytokine regulation in CRS.
文摘Chimeric antigen receptor(CAR)T-cell therapy is an effective new treatment strategy for hematologic malignancies.The success of CAR T-cell therapy in treating leukemia and lymphoma has promoted its development for multiple myeloma(MM),and the initial results of CAR T cell therapy have been encouraging.CAR T-cell therapy target antigens that have been clinically evaluated in MM;these antigens include CD19,B cell maturation antigen(BCMA),CD38,and CD138.A barrier to the widespread use of CAR T-cell therapy is its toxicity,primarily cytokine release syndrome(CRS),and neurologic toxicity.This study reports a patient with refractory MM who also developed megakaryocyte aplastic thrombocytopenia after receiving CAR T-cell therapy;such a case or the unusual side effects involving medications are yet unreported.There are risks in using cyclosporine and other immunosuppressants that may lead to MM recurrence as the use of such substances is contradictory to previous treatments;therefore,we temporarily administered platelet infusion as supportive care.Thus far,the condition of the patient has been steady and the patient regularly takes blood test in the hospital.
文摘The treatment of gastrointestinal cancer has always been a crucial research area,and targeted therapy has been receiving increasing attention.At present,the effect of targeted therapy is unsatisfactory for gastric cancer.Thus,the discovery of new targets is crucial.Claudin 18.2(CLDN18.2),a member of the claudin family,belongs to the tight junction protein family that controls the flow of molecules between cell layers.CLDN18.2 expression has been discussed in many studies.In recent years,there have been many studies on targeted therapy with CLDN18.2-ideal monoclonal antibody 362.Furthermore,CLDN18.2-specific chimeric antigen receptor T therapy has been used for CLDN18.2-positive tumors,such as gastric and pancreatic cancers.Considerable research has been focused on CLDN18.2.CLDN18.2,a newly discovered marker for precise targeted therapy of gastric cancer,could offer new hope for the treatment of gastric cancer.
基金funded by the State Key Laboratory of Medical Genomics,the Double First-Class Project(No.WF510162602)from the Ministry of Educationthe Shanghai Collaborative Innovation Program on Regenerative Medicine and Stem Cell Research(No.2019CXJQ01)+5 种基金the Overseas Expertise Introduction Project for Discipline Innovation(111 ProjectNo.B17029)the National Natural Science Foundation of China(Nos.82070227,81861148030,81670147,and 81970189)Clinical Research Plan of SHDC(No.SHDC2020CR2066B)the Shanghai Major Project for Clinical Medicine(No.2017ZZ01002)the Innovative Research Team of High-level Local Universities in Shanghai,National Science and Technology Major Project(No.2019ZX09301139).
文摘The current standard of care in hematological malignancies has brought considerable clinical benefits to patients.However,important bottlenecks still limit optimal achievements following a current medical practice.The genetic complexity of the diseases and the heterogeneity of tumor clones cause difficulty in ensuring long-term efficacy of conventional treatments for most hematological disorders.Consequently,new treatment strategies are necessary to improve clinical outcomes.Chimeric antigen receptor T-cell(CAR T)immunotherapy opens a new path for targeted therapy of hematological malignancies.In this review,through a representative case study,we summarize the current experience of CAR T-cell therapy,the management of common side effects,the causative mechanisms of therapy resistance,and new strategies to improve the efficacy of CAR T-cell therapy.
基金supported by grants from the National Key R&D Program of China(Nos.2021YFC2301900 and 2021YFC2301905)the National Natural Science Foundation of China(Nos.NSFC,81974303 and 82072271)+3 种基金Beijing Natural Science Foundation(Nos.L222068 and Z220018)the High-Level Public Health Specialized Talents Project of Beijing Municipal Health Commission(Nos.2022-2-018 and 2022-1-007)the Climbing the peak(Dengfeng)Talent Training Program of Beijing Hospitals Authority(Nos.DFL20191701)the Beijing Health Technologies Promotion Program(BHTPP202002)and Beijing Key Laboratory for HIV/AIDS Research(No.BZ0089).
文摘Although antiretroviral therapy(ART)can reduce the viral load in the plasma to undetectable levels in human immunodeficiency virus(HIV)-infected individuals,ART alone cannot completely eliminate HIV due to its integration into the host cell genome to form viral reservoirs.To achieve a functional cure for HIV infection,numerous preclinical and clinical studies are underway to develop innovative immunotherapies to eliminate HIV reservoirs in the absence of ART.Early studies have tested adoptive T-cell therapies in HIV-infected individuals,but their effectiveness was limited.In recent years,with the technological progress and great success of chimeric antigen receptor(CAR)therapy in the treatment of hematological malignancies,CAR therapy has gradually shown its advantages in the field of HIV infection.Many studies have identified a variety of HIV-specific CAR structures and types of cytolytic effector cells.Therefore,CAR therapy may be beneficial for enhancing HIV immunity,achieving HIV control,and eliminating HIV reservoirs,gradually becoming a promising strategy for achieving a functional HIV cure.In this review,we provide an overview of the design of anti-HIV CAR proteins,the cell types of anti-HIV CAR(including CAR T cells,CAR natural killer cells,and CAR-encoding hematopoietic stem/progenitor cells),the clinical application of CAR therapy in HIV infection,and the prospects and challenges in anti-HIV CAR therapy for maintaining viral suppression and eliminating HIV reservoirs.
文摘The ability to control mammalian cells such that they self-organize or enact therapeutic effects as desired has incredible implications.Not only would it further our understanding of native processes such as development and the immune response,but it would also have powerful applications in medical fields such as regenerative medicine and immunotherapy.This control is typically obtained by synthetic circuits that use synthetic receptors,but control remains incomplete.The synthetic juxtacrine receptors(SJRs)are widely used as they are fully modular and enable spatial control,but they have limited gene expression amplification and temporal control.As these are integral facets to cell control,I therefore designed transcription factor based amplifiers that amplify gene expression and enable unidirectional temporal control by prolonging duration of target gene expression.Using a validated in silico framework for SJR signaling,I combined these amplifiers with SJRs and show that these SJR amplifier circuits can direct spatiotemporal patterning and improve the quality of self-organization.I then show that these circuits can improve chimeric antigen receptor(CAR)T cell tumor killing against various heterogenous antigen expression tumors.These amplifiers are flexible tools that improve control over SJR based circuits with both basic and therapeutic applications.
文摘Malignant mesothelioma(MM)is a rare,aggressive solid tumor with limited therapeutic options and poor therapeutic response.The role of immunotherapy in MM is now well established and therapeutic options,such as checkpoint inhibitors,are increasingly being approved.Chimeric antigen receptor(CAR)-T cell therapy is successfully implemented in several hematologic cancers,but currently has inadequate effect in solid tumors,owing to several limitations,such as trafficking and infiltration,limited T cell persistence and exhaustion,the immunosuppressive TME and tumor antigen heterogeneity.The lack of uniform and universal expression of tumor-associated antigens(TAAs)on tumor cells,as well as TAA heterogeneity following tumor editing post-therapy,are issues of significant importance to CAR-T cell and associated antigen-targeting therapies.Our review discusses the concept of tumor antigen heterogeneity in MM,the consequences for CAR-T cell therapies and the strategies to overcome it.
文摘Chimeric antigen receptor(CAR)T cell therapy is a relatively new form of targeted therapy that has demonstrated impressive success in treating hematological malignancies.It has been challenging to translate this success to solid tumors.Reasons for this include barriers to delivery,tumor heterogeneity,cancer cells'ability to evade the immune system as well as identifying the optimal target.Most CAR T clinical trials have targeted well‐characterized cancer targets with significant preclinical and in some cases clinical validation.Published results from some of these trials show signs of anti‐cancer activity that warrant encouragement,but also caution,given instances of unacceptable toxicity.The narrow therapeutic window is complicated by the ability of CAR T cells to expand in patients regardless of dose.Here,we review those trials showing encouraging results in the context of target selection.It is clear that more specific tumor targeting is required,either by affinity tuning to avoid low‐level target expression in healthy cells,logic gating,or the identification of new targets that are more cancer specific.
基金financially supported by the Ministerio de Economia y Competitividad(BIO2017-84974-R)Xunta de Galicia"Grupo Referencia Competitiva 2016"(ED431C2016/041)the European Union(European Regional Developm ent Fund,Ref.ED431G2019/06).
文摘The immune system is a fascinating world of cells,soluble factors,interacting cells,and tissues,all of which are interconnected.The highly complex nature of the immune system makes it difficult to view it as a whole,but researchers are now trying to put all the pieces of the puzzle together to obtain a more complete picture.The development of new specialized equipment and immunological techniques,genetic approaches,animal models,and a long list of monoclonal antibodies,among many other factors,are improving our knowledge of this sophisticated system.The different types of cell subsets,soluble factors,membrane molecules,and cell functionalities are some aspects that we are starting to understand,together with their roles in health,aging,and illness.This knowledge is filling many of the gaps,and in some cases,it has led to changes in our previous assumptions;e.g.,adaptive immune cells were previously thought to be unique memory cells until trained innate immunity was observed,and several innate immune cells with features similar to those of cytokine-secreting T cells have been discovered.Moreover,we have improved our knowledge not only regarding immune-mediated illnesses and how the immune system works and interacts with other systems and components(such as the microbiome)but also in terms of ways to manipulate this system through immunotherapy.The development of different types of immunotherapies,including vaccines(prophylactic and therapeutic),and the use of pathogens,m onodonal antibodies,recombinant proteins,cytokines,and cellular immunotherapies,are changing the way in which we approach many diseases,especially cancer.
文摘Multiple myeloma(MM),considered an incurable hematological malignancy,is characterized by its clonal evolution of malignant plasma cells.Although the application of autologous stem cell transplantation(ASCT)and the introduction of novel agents such as immunomodulatory drugs(IMiDs)and proteasome inhibitors(PIs)have doubled the median overall survival to eight years,relapsed and refractory diseases are still frequent events in the course of MM.To achieve a durable and deep remission,immunotherapy modalities have been developed for relapsed/refractory multiple myeloma(RRMM).Among these approaches,chimeric antigen receptor(CAR)T-cell therapy is the most promising star,based on the results of previous success in B-cell neoplasms.In this immunotherapy,autologous T cells are engineered to express an artificial receptor which targets a tumor-associated antigen and initiates the T-cell killing procedure.Tisagenlecleucel and Axicabtagene,targeting the CD19 antigen,are the two pacesetters of CAR T-cell products.They were approved by the US Food and Drug Administration(FDA)in 2017 for the treatment of acute lymphocytic leukemia(ALL)and diffuse large B-cell lymphoma(DLBCL).Their development enabled unparalleled efficacy in combating hematopoietic neoplasms.In this review article,we summarize six promising candidate antigens in MM that can be targeted by CARs and discuss some noteworthy studies of the safety profile of current CAR T-cell therapy.