title: Effective response and delayed toxicities of refractory advanced diffuse large B-cell lymphoma treated by CD20-directed chimeric antigen receptor-modified T cells.
abstract: We conducted a trial testing a CD20-specific CAR coupled with CD137 and the CD3ζ moiety in patients with chemotherapy refractory advanced diffuse large B cell lymphomas (DLBCL). Seven patients were enrolled. One of the two patients with no bulky tumor obtained a 14-month durable and ongoing complete remission by cell infusion only, and another attained a 6-month tumor regression. Four of five patients with bulky tumor burden were evaluable for clinical efficacy, three of which attained 3- to 6-month tumor regression. Delayed toxicities related to cell infusion are directly correlated to tumor burden and tumor-harboring sites, and mainly included cytokine release symptoms, tumor lysis symptoms, massive hemorrhage of the alimentary tract and aggressive intrapulmonary inflammation surrounding extranodal lesions. These results show firstly that anti-CD20 CART cells can cause prolonged tumor regression in combination with debulking conditioning regimens for advanced DLBCL. This study is registered at www.clinicaltrials.gov as NCT01735604.
authors.affiliation: Department of Immunology, Institute of Basic Medicine, School of Life Sciences, Chinese PLA General Hospital, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Bio-therapeutic, Chinese PLA General Hospital, China.
authors.forename: Wen-ying
authors.initials: WY
authors.lastname: Zhang
authors.affiliation: Department of Immunology, Institute of Basic Medicine, School of Life Sciences, Chinese PLA General Hospital, China.
authors.forename: Qing-wang
authors.initials: QW
authors.lastname: Han
authors.affiliation: Department of Geriatric Hematology, Chinese PLA General Hospital, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Immunology, Institute of Basic Medicine, School of Life Sciences, Chinese PLA General Hospital, China.
authors.forename: Han-ren
authors.initials: HR
authors.lastname: Dai
authors.affiliation: Department of Immunology, Institute of Basic Medicine, School of Life Sciences, Chinese PLA General Hospital, China.
authors.forename: Ye-lei
authors.initials: YL
authors.lastname: Guo
authors.affiliation: Department of Hematology, Chinese PLA General Hospital, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Bo
authors.affiliation: Department of Bio-therapeutic, Chinese PLA General Hospital, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Fan
authors.affiliation: Department of Bio-therapeutic, Chinese PLA General Hospital, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Bio-therapeutic, Chinese PLA General Hospital, China.
authors.forename: Ya-jing
authors.initials: YJ
authors.lastname: Zhang
authors.affiliation: Department of Bio-therapeutic, Chinese PLA General Hospital, China.
authors.forename: Mei-xia
authors.initials: MX
authors.lastname: Chen
authors.affiliation: Department of Bio-therapeutic, Chinese PLA General Hospital, China.
authors.forename: Kai-chao
authors.initials: KC
authors.lastname: Feng
authors.affiliation: Department of Hematology, Chinese PLA General Hospital, China.
authors.forename: Quan-shun
authors.initials: QS
authors.lastname: Wang
authors.affiliation: Department of Immunology, Institute of Basic Medicine, School of Life Sciences, Chinese PLA General Hospital, China.
authors.forename: Xiao-bing
authors.initials: XB
authors.lastname: Fu
authors.affiliation: Department of Immunology, Institute of Basic Medicine, School of Life Sciences, Chinese PLA General Hospital, China. Electronic address: hanwdrsw69@yahoo.com.
authors.forename: Wei-dong
authors.initials: WD
authors.lastname: Han
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D018951:Antigens, CD20 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D002460:Cell Line; D003131:Combined Modality Therapy; D003602:Cytotoxicity, Immunologic; D005260:Female; D018628:Gene Dosage; D023061:Gene Order; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000009:adverse effects; D018655:Lymphocyte Count; D016403:Lymphoma, Large B-Cell, Diffuse / Q000175:diagnosis / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D049268:Positron-Emission Tomography; D011485:Protein Binding; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D037182:T-Cell Antigen Receptor Specificity / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9 / Q000235:genetics / Q000276:immunology / Q000378:metabolism
chemical_list: D018951:Antigens, CD20; D011948:Receptors, Antigen, T-Cell; D011993:Recombinant Fusion Proteins; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9
keywords: Anti-CD20 chimeric antigen receptor (CAR) T cells;; Delayed toxicities; Diffuse large B-cell lymphoma (DLBCL);; Refractory advanced;