CD19/BAFF-R dual-targeted CAR T cells for the treatment of mixed antigen-negative variants of acute lymphoblastic leukemia

Xiuli Wang, Zhenyuan Dong, Dennis Awuah, Wen Chung Chang, Wesley A. Cheng, Vibhuti Vyas, Soung Chul Cha, Aaron J. Anderson, Tiantian Zhang, Zhe Wang, Szymon J. Szymura, Benjamin Z. Kuang, Mary C. Clark, Ibrahim Aldoss, Stephen J. Forman, Larry W. Kwak, Hong Qin

Research output: Contribution to journalArticlepeer-review


Chimeric antigen receptor (CAR) T cells targeting CD19 mediate potent antitumor effects in B-cell malignancies including acute lymphoblastic leukemia (ALL), but antigen loss remains the major cause of treatment failure. To mitigate antigen escape and potentially improve the durability of remission, we developed a dual-targeting approach using an optimized, bispecific CAR construct that targets both CD19 and BAFF-R. CD19/BAFF-R dual CAR T cells exhibited antigen-specific cytokine release, degranulation, and cytotoxicity against both CD19−/− and BAFF-R−/− variant human ALL cells in vitro. Immunodeficient mice engrafted with mixed CD19−/− and BAFF-R−/− variant ALL cells and treated with a single dose of CD19/BAFF-R dual CAR T cells experienced complete eradication of both CD19−/− and BAFF-R−/− ALL variants, whereas mice treated with monospecific CD19 or BAFF-R CAR T cells succumbed to outgrowths of CD19−/BAFF-R+ or CD19+/BAFF-R− tumors, respectively. Further, CD19/BAFF-R dual CAR T cells showed prolonged in vivo persistence, raising the possibility that these cells may have the potential to promote durable remissions. Together, our data support clinical translation of BAFF-R/CD19 dual CAR T cells to treat ALL.

Original languageEnglish (US)
Pages (from-to)1015-1024
Number of pages10
Issue number4
StatePublished - Apr 2022

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research


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