title: Equipping CAR-modified T cells with a brake to prevent chronic adverse effects.
abstract: Genetical modification of T lymphocytes by chimeric antigen receptor (CAR), which has the affinity to tumor associated antigen (TAA), can redirect the normal T lymphocytes with tumor specificity. Through optimization of the CAR construct from first generation to third generation, the properties of these CAR-modified T lymphocytes, including, cytokines release, proliferative capacity, in vivo survival time, have been remarkably improved. These improvements accelerate the clinical applications of the CAR-modified T lymphocytes. Due to CD19, and CD20 specificity, CAR-modified T lymphocytes have been clinically used to treat leukemia. Notably, T lymphocytes genetically engineered by Carl June group with CAR targeting to CD19 have expanded more than 1,000 folds by clearing all CD19 positive leukemia cells, even the normal B cells, which infiltrated in bone marrow, and survived for more than 6 months. This encouraging report demonstrates the overwhelming tumor-lytic ability of the CAR-modified T lymphocytes; it also raises the concern about the chronic toxicity. Here, we emphasize the safety concern when using the CAR-modified T lymphocytes. We also summarize strategies exploited to clear the genetically engineered T lymphocytes under an urgent condition, which increases the safety and optimizes the applications of the CAR-modified T lymphocytes.
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Sichuan, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Yongsheng
authors.initials: Y
authors.lastname: Wang
mesh_terms: D058846:Antibodies, Monoclonal, Murine-Derived / Q000494:pharmacology; D018941:Antigens, CD19 / Q000235:genetics / Q000378:metabolism*; D018951:Antigens, CD20 / Q000235:genetics / Q000378:metabolism; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology; D049109:Cell Proliferation; D002470:Cell Survival; D005818:Genetic Engineering; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000009:adverse effects* / Q000379:methods; D007938:Leukemia / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D012307:Risk Factors; D000069283:Rituximab; D013601:T-Lymphocytes / Q000378:metabolism* / Q000473:pathology
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D018941:Antigens, CD19; D018951:Antigens, CD20; D000970:Antineoplastic Agents; D000069283:Rituximab