title: The novel anti-CD19 chimeric antigen receptors with humanized scFv (single-chain variable fragment) trigger leukemia cell killing.
abstract: The molecular design of CARs (Chimeric Antigen Receptors), especially the scFv, has been a major part to use of CAR-T cells for targeted adoptive immunotherapy. To address this issue, we chose a vector backbone encoding a second-generation CAR based on efficacy of a murine scFv-based CAR. Next, we generated a panel of humanized scFvs and tested in vitro for their ability to direct CAR-T cells to specifically lyse, proliferate, and secrete cytokines in response to antigen-bearing targets. Furthermore, in a xenograft model of lymphoma, human T cells expressing humanized scFvs exhibited the same anti-tumor efficacy as those expressing murine scFv and prolonged survival compared with cells expressing control CAR. Therefore, we uncovered CARs expressing humanized scFv domain that contribute the similar enhanced antileukemic efficacy and survival in tumor bearing mice. These results provide the basis for the future clinical studies of CAR-T cells transduced with humanized scFv directed to CD19.
authors.affiliation: Department of Hematology, Navy General Hospital, No. 6 Fucheng Road, Haidian District, Beijing 100048, China.
authors.forename: Liren
authors.initials: L
authors.lastname: Qian
authors.affiliation: Department of Health Management, Navy General Hospital, No. 6 Fucheng Road, Haidian District, Beijing 100048, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Li
authors.affiliation: Department of Respiration, Navy General Hospital, No. 6 Fucheng Road, Haidian District, Beijing 100048, China.
authors.forename: Lie
authors.initials: L
authors.lastname: Ma
authors.affiliation: Beijing Immunochina Medical Science & Technology Co., Ltd., No. 8 Shengmingyuan Road, Changping District, Beijing 102200, China.
authors.forename: Ting
authors.initials: T
authors.lastname: He
authors.affiliation: Beijing Immunochina Medical Science & Technology Co., Ltd., No. 8 Shengmingyuan Road, Changping District, Beijing 102200, China.
authors.forename: Feifei
authors.initials: F
authors.lastname: Qi
authors.affiliation: Department of Hematology, Navy General Hospital, No. 6 Fucheng Road, Haidian District, Beijing 100048, China. Electronic address: nghxyk@163.com.
authors.forename: Jianliang
authors.initials: J
authors.lastname: Shen
authors.affiliation: Beijing Immunochina Medical Science & Technology Co., Ltd., No. 8 Shengmingyuan Road, Changping District, Beijing 102200, China. Electronic address: luxinan@immunochina.com.
authors.forename: Xin-An
authors.initials: XA
authors.lastname: Lu
mesh_terms: D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000235:genetics; D018941:Antigens, CD19 / Q000276:immunology; D017209:Apoptosis; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D007938:Leukemia / Q000276:immunology / Q000628:therapy*; D008213:Lymphocyte Activation; D051379:Mice; D016513:Mice, SCID; D009374:Neoplasms, Experimental / Q000276:immunology / Q000628:therapy*; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000235:genetics; D057127:Single-Chain Antibodies / Q000235:genetics / Q000378:metabolism*; D013601:T-Lymphocytes / Q000502:physiology* / Q000637:transplantation; D023041:Xenograft Model Antitumor Assays
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D018941:Antigens, CD19; D016207:Cytokines; D011948:Receptors, Antigen, T-Cell; D011993:Recombinant Fusion Proteins; D057127:Single-Chain Antibodies
keywords: CARs; Humanization; Xenograft; scFv