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Design and preclinical testing of an anti-CD41 CAR T cell for the treatment of acute megakaryoblastic leukaemia.
Tigu, Adrian Bogdan; Constantinescu, Catalin Sorin; Teodorescu, Patric; Kegyes, David; Munteanu, Raluca; Feder, Richard; Peters, Mareike; Pralea, Ioana; Iuga, Cristina; Cenariu, Diana; Marcu, Andra; Tanase, Alina; Colita, Anca; Drula, Rares; Bergthorsson, Jon Thor; Greiff, Victor; Dima, Delia; Selicean, Cristina; Rus, Ioana; Zdrenghea, Mihnea; Gulei, Diana; Ghiaur, Gabriel; Tomuleasa, Ciprian.
Afiliación
  • Tigu AB; Medfuture Research Center for Advanced Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania.
  • Constantinescu CS; Medfuture Research Center for Advanced Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania.
  • Teodorescu P; Department of Hematology, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania.
  • Kegyes D; Intensive Care Unit, Emergency Clinical Hospital, Cluj-Napoca, Romania.
  • Munteanu R; Department of Hematology, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania.
  • Feder R; Department of Leukemia, Sidney Kimmel Cancer Center at Johns Hopkins, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
  • Peters M; Medfuture Research Center for Advanced Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania.
  • Pralea I; Department of Hematology, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania.
  • Iuga C; Medfuture Research Center for Advanced Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania.
  • Cenariu D; Medfuture Research Center for Advanced Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania.
  • Marcu A; Medfuture Research Center for Advanced Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania.
  • Tanase A; Department of Hematology, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania.
  • Colita A; Medfuture Research Center for Advanced Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania.
  • Drula R; Medfuture Research Center for Advanced Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania.
  • Bergthorsson JT; Department of Drug Analysis, School of Pharmacy, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania.
  • Greiff V; Medfuture Research Center for Advanced Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania.
  • Dima D; Department of Pediatrics, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania.
  • Selicean C; Department of Stem Cell Transplantation, Fundeni Clinical Institute, Bucharest, Romania.
  • Rus I; Department of Pediatrics, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania.
  • Zdrenghea M; Department of Stem Cell Transplantation, Fundeni Clinical Institute, Bucharest, Romania.
  • Gulei D; Department of Pediatrics, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania.
  • Ghiaur G; Department of Stem Cell Transplantation, Fundeni Clinical Institute, Bucharest, Romania.
  • Tomuleasa C; Medfuture Research Center for Advanced Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania.
J Cell Mol Med ; 27(19): 2864-2875, 2023 Oct.
Article en En | MEDLINE | ID: mdl-37667538
Acute megakaryoblastic leukaemia (AMkL) is a rare subtype of acute myeloid leukaemia (AML) representing 5% of all reported cases, and frequently diagnosed in children with Down syndrome. Patients diagnosed with AMkL have low overall survival and have poor outcome to treatment, thus novel therapies such as CAR T cell therapy could represent an alternative in treating AMkL. We investigated the effect of a new CAR T cell which targets CD41, a specific surface antigen for M7-AMkL, against an in vitro model for AMkL, DAMI Luc2 cell line. The performed flow cytometry evaluation highlighted a percentage of 93.8% CAR T cells eGFP-positive and a limited acute effect on lowering the target cell population. However, the interaction between effector and target (E:T) cells, at a low ratio, lowered the cell membrane integrity, and reduced the M7-AMkL cell population after 24 h of co-culture, while the cytotoxic effect was not significant in groups with higher E:T ratio. Our findings suggest that the anti-CD41 CAR T cells are efficient for a limited time spawn and the cytotoxic effect is visible in all experimental groups with low E:T ratio.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Prognostic_studies Idioma: En Revista: J Cell Mol Med Asunto de la revista: BIOLOGIA MOLECULAR Año: 2023 Tipo del documento: Article País de afiliación: Rumanía Pais de publicación: Reino Unido

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Prognostic_studies Idioma: En Revista: J Cell Mol Med Asunto de la revista: BIOLOGIA MOLECULAR Año: 2023 Tipo del documento: Article País de afiliación: Rumanía Pais de publicación: Reino Unido