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CAR T cells targeting BAFF-R can overcome CD19 antigen loss in B cell malignancies

Qin, H; Dong, Z; Wang, X; Cheng, WA; Wen, F; Xue, W; Sun, H; ... Kwak, LW; + view all (2019) CAR T cells targeting BAFF-R can overcome CD19 antigen loss in B cell malignancies. Science Translational Medicine , 11 (511) , Article eaaw9414. 10.1126/scitranslmed.aaw9414. Green open access

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Abstract

CAR T cells targeting CD19 provide promising options for treatment of B cell malignancies. However, tumor relapse from antigen loss can limit efficacy. We developed humanized, second-generation CAR T cells against another B cell–specific marker, B cell activating factor receptor (BAFF-R), which demonstrated cytotoxicity against human lymphoma and acute lymphoblastic leukemia (ALL) lines. Adoptively transferred BAFF-R-CAR T cells eradicated 10-day preestablished tumor xenografts after a single treatment and retained efficacy against xenografts deficient in CD19 expression, including CD19-negative variants within a background of CD19-positive lymphoma cells. Four relapsed, primary ALLs with CD19 antigen loss obtained after CD19-directed therapy retained BAFF-R expression and activated BAFF-R-CAR, but not CD19-CAR, T cells. BAFF-R-CAR, but not CD19-CAR, T cells also demonstrated antitumor effects against an additional CD19 antigen loss primary patient–derived xenograft (PDX) in vivo. BAFF-R is amenable to CAR T cell therapy, and its targeting may prevent emergence of CD19 antigen loss variants.

Type: Article
Title: CAR T cells targeting BAFF-R can overcome CD19 antigen loss in B cell malignancies
Open access status: An open access version is available from UCL Discovery
DOI: 10.1126/scitranslmed.aaw9414
Publisher version: https://doi.org/10.1126/scitranslmed.aaw9414
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
UCL classification: UCL
UCL > Provost and Vice Provost Offices > UCL BEAMS
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Biochemical Engineering
URI: https://discovery.ucl.ac.uk/id/eprint/10085975
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