title: Current status and regulatory perspective of chimeric antigen receptor-modified T cell therapeutics.
abstract: Chimeric antigen receptor-modified T cells (CAR-T) have emerged as a new modality for cancer immunotherapy due to their potent efficacy against terminal cancers. CAR-Ts are reported to exert higher efficacy than monoclonal antibodies and antibody-drug conjugates, and act via mechanisms distinct from T cell receptor-engineered T cells. These cells are constructed by transducing genes encoding fusion proteins of cancer antigen-recognizing single-chain Fv linked to intracellular signaling domains of T cell receptors. CAR-Ts are classified as first-, second- and third-generation, depending on the intracellular signaling domain number of T cell receptors. This review covers the current status of CAR-T research, including basic proof-of-concept investigations at the cell and animal levels. Currently ongoing clinical trials of CAR-T worldwide are additionally discussed. Owing to the lack of existing approved products, several unresolved concerns remain with regard to safety, efficacy and manufacturing of CAR-T, as well as quality control issues. In particular, the cytokine release syndrome is the major side-effect impeding the successful development of CAR-T in clinical trials. Here, we have addressed the challenges and regulatory perspectives of CAR-T therapy.
authors.affiliation: College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Republic of Korea.
authors.forename: Mi-Gyeong
authors.initials: MG
authors.lastname: Kim
authors.affiliation: College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Republic of Korea.
authors.forename: Dongyoon
authors.initials: D
authors.lastname: Kim
authors.affiliation: Advanced Therapy Product Research Division, National Institute of Food and Drug Safety, Cheongju, Chungcheongbuk-do, Republic of Korea.
authors.forename: Soo-Kyung
authors.initials: SK
authors.lastname: Suh
authors.affiliation: Advanced Therapy Product Research Division, National Institute of Food and Drug Safety, Cheongju, Chungcheongbuk-do, Republic of Korea.
authors.forename: Zewon
authors.initials: Z
authors.lastname: Park
authors.affiliation: College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Republic of Korea.|Cell and Gene Therapeutics Division, National Institute of Food and Drug Safety, Cheongju, Chungcheongbuk-do, Republic of Korea.
authors.forename: Min Joung
authors.initials: MJ
authors.lastname: Choi
authors.affiliation: College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Republic of Korea. ohyk@snu.ac.kr.
authors.forename: Yu-Kyoung
authors.initials: YK
authors.lastname: Oh
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology*; D002986:Clinical Trials as Topic / Q000331:legislation & jurisprudence; D004345:Drug Industry / Q000331:legislation & jurisprudence; D033161:Government Regulation; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000331:legislation & jurisprudence / Q000379:methods*; D009369:Neoplasms / Q000276:immunology / Q000628:therapy; D011786:Quality Control; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D000951:Antigens, Neoplasm; D011948:Receptors, Antigen, T-Cell; D011993:Recombinant Fusion Proteins
keywords: Chimeric antigen receptor-modified T cells; Clinical trials; Efficacy; Manufacture; Regulatory perspective; Safety