Novel anti-CD3 chimeric antigen receptor targeting of aggressive T cell malignancies

Kevin H. Chen, Masayuki Wada, Amelia E. Firor, Kevin G. Pinz, Alexander Jares, Hua Liu, Huda Shafic Salman, Marc Golightly, Fengshuo Lan, Xun Jiang, Yupo Ma

Research output: Contribution to journalArticle

29 Scopus citations

Abstract

Peripheral T-cell lymphomas (PTCLS) comprise a diverse group of difficult to treat, very aggressive non-Hodgkin's lymphomas (NHLS) with poor prognoses and dismal patient outlook. Despite the fact that PTCLs comprise the majority of T-cell malignancies, the standard of care is poorly established. Chimeric antigen receptor (CAR) immunotherapy has shown in B-cell malignancies to be an effective curative option and this extends promise into treating T-cell malignancies. Because PTCLS frequently develop from mature T-cells, CD3 is similarly strongly and uniformly expressed in many PTCL malignancies, with expression specific to the hematological compartment thus making it an attractive target for CAR design. We engineered a robust 3rd generation anti-CD3 CAR construct (CD3CAR) into an NK cell line (NK-92). We found that CD3CAR NK-92 cells specifically and potently lysed diverse CD3+ human PTCL primary samples as well as T-cell leukemia cells lines ex vivo. Furthermore, CD3CAR NK-92 cells effectively controlled and suppressed Jurkat tumor cell growth in vivo and significantly prolonged survival. In this study, we present the CAR directed targeting of a novel target - CD3 using CAR modified NK-92 cells with an emphasis on efficacy, specificity, and potential for new therapeutic approaches that could improve the current standard of care for PTCLs.

Original languageEnglish (US)
Pages (from-to)56219-56232
Number of pages14
JournalOncotarget
Volume7
Issue number35
DOIs
StatePublished - Jan 1 2016

Keywords

  • CD3CAR
  • Immunotherapy
  • NK cells
  • T cell malignancies

ASJC Scopus subject areas

  • Oncology

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    Chen, K. H., Wada, M., Firor, A. E., Pinz, K. G., Jares, A., Liu, H., Salman, H. S., Golightly, M., Lan, F., Jiang, X., & Ma, Y. (2016). Novel anti-CD3 chimeric antigen receptor targeting of aggressive T cell malignancies. Oncotarget, 7(35), 56219-56232. https://doi.org/10.18632/oncotarget.11019