Preclinical targeting of aggressive T-cell malignancies using anti-CD5 chimeric antigen receptor

K. H. Chen, M. Wada, K. G. Pinz, H. Liu, K. W. Lin, A. Jares, A. E. Firor, X. Shuai, Huda Shafic Salman, M. Golightly, F. Lan, L. Senzel, E. L. Leung, X. Jiang, Y. Ma

Research output: Contribution to journalArticle

54 Scopus citations

Abstract

The outlook for T-cell malignancies remain poor due to the lack of effective therapeutic options. Chimeric antigen receptor (CAR) immunotherapy has recently shown promise in clinical trials for B-cell malignancies, however, designing CARs for T-cell based disease remain a challenge due to the shared surface antigen pool between normal and malignant T-cells. Normal T-cells express CD5 but NK (natural killer) cells do not, positioning NK cells as attractive cytotoxicity cells for CD5CAR design. Additionally, CD5 is highly expressed in T-cell acute lymphoblastic leukemia (T-ALL) and peripheral T-cell lymphomas (PTCLs). Here, we report a robust anti-CD5 CAR (CD5CAR) transduced into a human NK cell line NK-92 that can undergo stable expansion ex vivo. We found that CD5CAR NK-92 cells possessed consistent, specific, and potent anti-tumor activity against a variety of T-cell leukemia and lymphoma cell lines as well as primary tumor cells. Furthermore, we were able to demonstrate significant inhibition and control of disease progression in xenograft mouse models of T-ALL. The data suggest that CAR redirected targeting for T-cell malignancies using NK cells may be a viable method for new and complementary therapeutic approaches that could improve the current outcome for patients.

Original languageEnglish (US)
Pages (from-to)2151-2160
Number of pages10
JournalLeukemia
Volume31
Issue number10
DOIs
StatePublished - Oct 1 2017

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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    Chen, K. H., Wada, M., Pinz, K. G., Liu, H., Lin, K. W., Jares, A., Firor, A. E., Shuai, X., Salman, H. S., Golightly, M., Lan, F., Senzel, L., Leung, E. L., Jiang, X., & Ma, Y. (2017). Preclinical targeting of aggressive T-cell malignancies using anti-CD5 chimeric antigen receptor. Leukemia, 31(10), 2151-2160. https://doi.org/10.1038/leu.2017.8