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 journalArticle

18 Citations (Scopus)

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

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Acute Myeloid Leukemia
T-Lymphocytes
Stem Cells
Recurrence
Interleukin-3 Receptor alpha Subunit
Sialic Acid Binding Ig-like Lectin 3
Antigens
Health Services Needs and Demand
Myeloid Cells
Disease Progression
Leukemia
Safety
Therapeutics
Population
Neoplasms

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

Cite this

Petrov, J. C., Wada, M., Pinz, K. G., Yan, L. E., Chen, K. H., Shuai, X., ... Ma, Y. (2018). Compound CAR T-cells as a double-pronged approach for treating acute myeloid leukemia. Leukemia, 32(6), 1317-1326. https://doi.org/10.1038/s41375-018-0075-3

Compound CAR T-cells as a double-pronged approach for treating acute myeloid leukemia. / Petrov, Jessica C.; Wada, Masayuki; Pinz, Kevin G.; Yan, Lulu E.; Chen, Kevin H.; Shuai, Xiao; Liu, Hua; Chen, Xi; Leung, Lai Han; Salman, Huda Shafic; Hagag, Nabil; Liu, Fang; Jiang, Xun; Ma, Yupo.

In: Leukemia, Vol. 32, No. 6, 01.06.2018, p. 1317-1326.

Research output: Contribution to journalArticle

Petrov, JC, Wada, M, Pinz, KG, Yan, LE, Chen, KH, Shuai, X, Liu, H, Chen, X, Leung, LH, Salman, HS, Hagag, N, Liu, F, Jiang, X & Ma, Y 2018, 'Compound CAR T-cells as a double-pronged approach for treating acute myeloid leukemia', Leukemia, vol. 32, no. 6, pp. 1317-1326. https://doi.org/10.1038/s41375-018-0075-3
Petrov JC, Wada M, Pinz KG, Yan LE, Chen KH, Shuai X et al. Compound CAR T-cells as a double-pronged approach for treating acute myeloid leukemia. Leukemia. 2018 Jun 1;32(6):1317-1326. https://doi.org/10.1038/s41375-018-0075-3
Petrov, Jessica C. ; Wada, Masayuki ; Pinz, Kevin G. ; Yan, Lulu E. ; Chen, Kevin H. ; Shuai, Xiao ; Liu, Hua ; Chen, Xi ; Leung, Lai Han ; Salman, Huda Shafic ; Hagag, Nabil ; Liu, Fang ; Jiang, Xun ; Ma, Yupo. / Compound CAR T-cells as a double-pronged approach for treating acute myeloid leukemia. In: Leukemia. 2018 ; Vol. 32, No. 6. pp. 1317-1326.
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