Targeting T-cell malignancies using anti-CD4 CAR NK-92 cells

Kevin G. Pinz, Elizabeth Yakaboski, Alexander Jares, Hua Liu, Amelia E. Firor, Kevin H. Chen, Masayuki Wada, Huda Shafic Salman, William Tse, Nabil Hagag, Fengshuo Lan, Elaine Lai Han Leung, Xun Jiang, Yupo Ma

Research output: Contribution to journalArticle

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Abstract

Peripheral T-cell lymphomas (PTCLs) are a group of very aggressive non- Hodgkin's lymphomas (NHLs) with poor prognoses and account for a majority of T-cell malignancies. Overall, the standard of care for patients with T-cell malignancies is poorly established, and there is an urgent clinical need for a new approach. As demonstrated in B-cell malignancies, chimeric antigen receptor (CAR) immunotherapy provides great hope as a curative treatment regimen. Because PTCLs develop from mature T-cells, these NHLs are commonly CD4+, and CD4 is highly and uniformly expressed. Therefore, CD4 is an ideal target for PTCL CAR immunotherapy. To that effect, we created a robust third-generation anti-CD4 CAR construct (CD4CAR) and introduced it into clonal NK cells (NK-92). CD4CAR NK-92 cells specifically and robustly eliminated diverse CD4+ human T-cell leukemia and lymphoma cell lines (KARPAS-299, CCRF-CEM, and HL60) and patient samples ex vivo. Furthermore, CD4CAR NK-92 cells effectively targeted KARPAS-299 cells in vivo that modeled difficult-to-access lymphoma nodules, significantly prolonging survival. In our study, we present novel targeting of CD4 using CAR-modified NK cells, and demonstrate efficacy. Combined, our data support CD4CAR NK cell immunotherapy as a potential new avenue for the treatment of PTCLs and CD4+ T-cell malignancies.

Original languageEnglish (US)
Pages (from-to)112783-112796
Number of pages14
JournalOncotarget
Volume8
Issue number68
DOIs
StatePublished - Jan 1 2017

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CD4 Antigens
Antigen Receptors
Peripheral T-Cell Lymphoma
Natural Killer Cells
T-Lymphocytes
Immunotherapy
Neoplasms
Non-Hodgkin's Lymphoma
Adult T Cell Leukemia Lymphoma
Standard of Care
Lymphoma
B-Lymphocytes
Cell Line
Survival
Therapeutics

Keywords

  • Chimeric antigen receptors
  • Immunotherapy
  • NK cells
  • T-cell malignancies

ASJC Scopus subject areas

  • Oncology

Cite this

Pinz, K. G., Yakaboski, E., Jares, A., Liu, H., Firor, A. E., Chen, K. H., ... Ma, Y. (2017). Targeting T-cell malignancies using anti-CD4 CAR NK-92 cells. Oncotarget, 8(68), 112783-112796. https://doi.org/10.18632/oncotarget.22626

Targeting T-cell malignancies using anti-CD4 CAR NK-92 cells. / Pinz, Kevin G.; Yakaboski, Elizabeth; Jares, Alexander; Liu, Hua; Firor, Amelia E.; Chen, Kevin H.; Wada, Masayuki; Salman, Huda Shafic; Tse, William; Hagag, Nabil; Lan, Fengshuo; Leung, Elaine Lai Han; Jiang, Xun; Ma, Yupo.

In: Oncotarget, Vol. 8, No. 68, 01.01.2017, p. 112783-112796.

Research output: Contribution to journalArticle

Pinz, KG, Yakaboski, E, Jares, A, Liu, H, Firor, AE, Chen, KH, Wada, M, Salman, HS, Tse, W, Hagag, N, Lan, F, Leung, ELH, Jiang, X & Ma, Y 2017, 'Targeting T-cell malignancies using anti-CD4 CAR NK-92 cells', Oncotarget, vol. 8, no. 68, pp. 112783-112796. https://doi.org/10.18632/oncotarget.22626
Pinz KG, Yakaboski E, Jares A, Liu H, Firor AE, Chen KH et al. Targeting T-cell malignancies using anti-CD4 CAR NK-92 cells. Oncotarget. 2017 Jan 1;8(68):112783-112796. https://doi.org/10.18632/oncotarget.22626
Pinz, Kevin G. ; Yakaboski, Elizabeth ; Jares, Alexander ; Liu, Hua ; Firor, Amelia E. ; Chen, Kevin H. ; Wada, Masayuki ; Salman, Huda Shafic ; Tse, William ; Hagag, Nabil ; Lan, Fengshuo ; Leung, Elaine Lai Han ; Jiang, Xun ; Ma, Yupo. / Targeting T-cell malignancies using anti-CD4 CAR NK-92 cells. In: Oncotarget. 2017 ; Vol. 8, No. 68. pp. 112783-112796.
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