In the past,there has been considerable focus on a host of drugs and chemicals that may produce colonic toxicity.Now,a variety of new biological monoclonal antibody agents,usually administered by infusion,have appeare...In the past,there has been considerable focus on a host of drugs and chemicals that may produce colonic toxicity.Now,a variety of new biological monoclonal antibody agents,usually administered by infusion,have appeared in the clinical realm over the last decade or so to treat different chronic inflammatory or malignant disorders.For some of these agents,adverse effects have been documented,including apparently new forms of immune-mediated inflammatory bowel disease.In some,only limited symptoms have been recorded,but in others,severe colitis with serious complications,such as bowel perforation has been recorded.In others,adverse effects may have a direct vascular or ischemic basis,while other intestinal effects may be related to a superimposed infection.Some new onset cases of ulcerative colitis or Crohn's disease may also be attributed to the same agents used to treat these diseases,or be responsible for disease exacerbation.Dramatic and well documented side effects have been observed with ipilimumab,a humanized monoclonal antibody developed to reduce and overcome cytotoxic T-lymphocyte antigen 4,a key negative feedback regulator of the T-cell anti-tumor response.This agent has frequently been used in the treatment of different malignancies,notably,malignant melanoma.Side effects with this agent occur in up to 40% and these are believed to be largely immune-mediated.One of these is a form of enterocolitis that may be severe,and occa-sionally,fatal.Other agents include rituximab(an antiCD20 monoclonal antibody),bevacizumab(a monoclonal antibody against the vascular endothelial growth factor) and anti-tumor necrosis factor agents,including infliximab,adalimumab and etanercept.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
文摘In the past,there has been considerable focus on a host of drugs and chemicals that may produce colonic toxicity.Now,a variety of new biological monoclonal antibody agents,usually administered by infusion,have appeared in the clinical realm over the last decade or so to treat different chronic inflammatory or malignant disorders.For some of these agents,adverse effects have been documented,including apparently new forms of immune-mediated inflammatory bowel disease.In some,only limited symptoms have been recorded,but in others,severe colitis with serious complications,such as bowel perforation has been recorded.In others,adverse effects may have a direct vascular or ischemic basis,while other intestinal effects may be related to a superimposed infection.Some new onset cases of ulcerative colitis or Crohn's disease may also be attributed to the same agents used to treat these diseases,or be responsible for disease exacerbation.Dramatic and well documented side effects have been observed with ipilimumab,a humanized monoclonal antibody developed to reduce and overcome cytotoxic T-lymphocyte antigen 4,a key negative feedback regulator of the T-cell anti-tumor response.This agent has frequently been used in the treatment of different malignancies,notably,malignant melanoma.Side effects with this agent occur in up to 40% and these are believed to be largely immune-mediated.One of these is a form of enterocolitis that may be severe,and occa-sionally,fatal.Other agents include rituximab(an antiCD20 monoclonal antibody),bevacizumab(a monoclonal antibody against the vascular endothelial growth factor) and anti-tumor necrosis factor agents,including infliximab,adalimumab and etanercept.
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.
