Research ArticleCancer

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

See allHide authors and affiliations

Science Translational Medicine  25 Sep 2019:
Vol. 11, Issue 511, eaaw9414
DOI: 10.1126/scitranslmed.aaw9414

You are currently viewing the abstract.

View Full Text

Log in to view the full text

Log in through your institution

Log in through your institution

Circumventing CD19 antigen loss

Chimeric antigen receptor (CAR) T cell treatment for B cell malignancies was pioneered with CD19-targeted CAR T cells. Despite robust clinical responses, relapse due to CD19 antigen loss is common. Qin et al. examined B cell activating factor receptor (BAFF-R) as an alternate CAR T cell target. BAFF-R–targeted CAR T cells could kill multiple human lymphoma and leukemia cell lines, either in vitro or in mice, as well as patient-derived samples. The BAFF-R-CAR T cells could also eradicate tumors lacking CD19. Their compelling preclinical results support the clinical development of BAFF-R–targeted CAR T cells for combating B cell malignancies.


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.

View Full Text

Stay Connected to Science Translational Medicine