Oncotarget

Research Papers:

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 Salman, Marc Golightly, Fengshuo Lan, Xun Jiang, _ Yupo Ma

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Abstract

Kevin H. Chen1,*, Masayuki Wada1,*, Amelia E. Firor1, Kevin G. Pinz1, Alexander Jares2, Hua Liu2, Huda Salman3, Marc Golightly2, Fengshuo Lan3, Xun Jiang1 and Yupo Ma1,2,4

1 iCell Gene Therapeutics LLC, Research & Development Division, Long Island High Technology Incubator, Stony Brook, NY, USA

2 Department of Pathology, Stony Brook Medicine, Stony Brook, NY, USA

3 Department of Internal Medicine, Stony Brook Medicine, Stony Brook University Medical Center, Stony Brook, NY, USA

4 Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology, Macau, China

* These authors have contributed equally to this work

Correspondence to:

Xun Jiang, email:

Yupo Ma, email:

Keywords: NK cells, immunotherapy, T cell malignancies, CD3CAR

Received: May 29, 2016 Accepted: July 22, 2016 Published: August 02, 2016

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.

Author Information

Kevin H. Chen

Masayuki Wada

Amelia E. Firor

Kevin G. Pinz

Alexander Jares

Hua Liu

Huda Salman

Marc Golightly

Fengshuo Lan

Xun Jiang
Primary Contact  _

Yupo Ma


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