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.
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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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