Compound CAR T-cells as a double-pronged approach for treating acute myeloid leukemia

Jessica C. Petrov, Masayuki Wada, Kevin G. Pinz, Lulu E. Yan, Kevin H. Chen, Xiao Shuai, Hua Liu, Xi Chen, Lai Han Leung, Huda Shafic Salman, Nabil Hagag, Fang Liu, Xun Jiang, Yupo Ma

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

Abstract

Acute myeloid leukemia (AML) bears heterogeneous cells that can consequently offset killing by single-CAR-based therapy, which results in disease relapse. Leukemic stem cells (LSCs) associated with CD123 expression comprise a rare population that also plays an important role in disease progression and relapse. Here, we report on the robust anti-tumor activity of a compound CAR (cCAR) T-cell possessing discrete scFv domains targeting two different AML antigens, CD123, and CD33, simultaneously. We determined that the resulting cCAR T-cells possessed consistent, potent, and directed cytotoxicity against each target antigen population. Using four leukemia mouse models, we found superior in vivo survival after cCAR treatment. We also designed an alemtuzumab safety-switch that allowed for rapid cCAR therapy termination in vivo. These findings indicate that targeting both CD123 and CD33 on AML cells may be an effective strategy for eliminating both AML bulk disease and LSCs, and potentially prevent relapse due to antigen escape or LSC persistence.

Original languageEnglish (US)
Pages (from-to)1317-1326
Number of pages10
JournalLeukemia
Volume32
Issue number6
DOIs
StatePublished - Jun 1 2018

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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