title: Novel anti-CD3 chimeric antigen receptor targeting of aggressive T cell malignancies.
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.
authors: iCell Gene Therapeutics LLC, Research & Development Division, Long Island High Technology Incubator, Stony Brook, NY, USA.
authors: Kevin H
authors: KH
authors: Chen
authors: iCell Gene Therapeutics LLC, Research & Development Division, Long Island High Technology Incubator, Stony Brook, NY, USA.
authors: Masayuki
authors: M
authors: Wada
authors: iCell Gene Therapeutics LLC, Research & Development Division, Long Island High Technology Incubator, Stony Brook, NY, USA.
authors: Amelia E
authors: AE
authors: Firor
authors: iCell Gene Therapeutics LLC, Research & Development Division, Long Island High Technology Incubator, Stony Brook, NY, USA.
authors: Kevin G
authors: KG
authors: Pinz
authors: Department of Pathology, Stony Brook Medicine, Stony Brook, NY, USA.
authors: Alexander
authors: A
authors: Jares
authors: Department of Pathology, Stony Brook Medicine, Stony Brook, NY, USA.
authors: Hua
authors: H
authors: Liu
authors: Department of Internal Medicine, Stony Brook Medicine, Stony Brook University Medical Center, Stony Brook, NY, USA.
authors: Huda
authors: H
authors: Salman
authors: Department of Pathology, Stony Brook Medicine, Stony Brook, NY, USA.
authors: Marc
authors: M
authors: Golightly
authors: Department of Internal Medicine, Stony Brook Medicine, Stony Brook University Medical Center, Stony Brook, NY, USA.
authors: Fengshuo
authors: F
authors: Lan
authors: iCell Gene Therapeutics LLC, Research & Development Division, Long Island High Technology Incubator, Stony Brook, NY, USA.
authors: Xun
authors: X
authors: Jiang
authors: iCell Gene Therapeutics LLC, Research & Development Division, Long Island High Technology Incubator, Stony Brook, NY, USA.|Department of Pathology, Stony Brook Medicine, Stony Brook, NY, USA.|Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology, Macau, China.
authors: Yupo
authors: Y
authors: Ma
mesh_terms: D000818:Animals; D017252:CD3 Complex / Q000276:immunology* / Q000378:metabolism; D018920:Coculture Techniques; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D019169:Jurkat Cells; D053208:Kaplan-Meier Estimate; D007694:Killer Cells, Natural / Q000276:immunology* / Q000637:transplantation; D016411:Lymphoma, T-Cell, Peripheral / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D008297:Male; D051379:Mice; D016513:Mice, SCID; D011948:Receptors, Antigen, T-Cell / Q000276:immunology* / Q000627:therapeutic use; D011993:Recombinant Fusion Proteins / Q000276:immunology / Q000627:therapeutic use; D023041:Xenograft Model Antitumor Assays
chemical_list: D017252:CD3 Complex; D011948:Receptors, Antigen, T-Cell; D011993:Recombinant Fusion Proteins
keywords: CD3CAR; NK cells; T cell malignancies; immunotherapy