Affordable Access

Access to the full text

Chimeric antigen-receptor (CAR) engineered natural killer cells in a chronic myeloid leukemia (CML) blast crisis model

Authors
  • Imeri, Jusuf1
  • Marcoux, Paul1
  • Huyghe, Matthias1
  • Desterke, Christophe1
  • Fantacini, Daianne Maciely Carvalho2
  • Griscelli, Frank1, 3, 4, 5
  • Covas, Dimas T.2, 6
  • de Souza, Lucas Eduardo Botelho2, 6
  • Griscelli, Annelise Bennaceur1, 3, 4, 7
  • Turhan, Ali G.1, 3, 4, 7
  • 1 INSERM UMR-S-1310, Université Paris Saclay, Villejuif, France and ESTeam Paris Sud, Université Paris Saclay, Villejuif , (France)
  • 2 Blood Center of Ribeirão Preto/Ribeirão Preto School of Medicine/University of São Paulo, Ribeirao Preto, SP , (Brazil)
  • 3 INGESTEM National iPSC Infrastructure, Villejuif , (France)
  • 4 CITHERA, Centre for IPSC Therapies, INSERM UMS-45, Evry , (France)
  • 5 Université Paris Descartes, Faculté Sorbonne Paris Cité, Faculté des Sciences Pharmaceutiques et Biologiques, Paris , (France)
  • 6 Biotechnology Nucleus of Ribeirão Preto/Butantan Institute - Ribeirão Preto, Ribeirao Preto, SP , (Brazil)
  • 7 APHP Paris Saclay, Department of Hematology, Hopital Bicetre & Paul Brousse, Villejuif , (France)
Type
Published Article
Journal
Frontiers in Immunology
Publisher
Frontiers Media SA
Publication Date
Jan 08, 2024
Volume
14
Identifiers
DOI: 10.3389/fimmu.2023.1309010
Source
Frontiers
Keywords
Disciplines
  • Immunology
  • Brief Research Report
License
Green

Abstract

During the last two decades, the introduction of tyrosine kinase inhibitors (TKIs) to the therapy has changed the natural history of CML but progression into accelerated and blast phase (AP/BP) occurs in 3-5% of cases, especially in patients resistant to several lines of TKIs. In TKI-refractory patients in advanced phases, the only curative option is hematopoietic stem cell transplantation. We and others have shown the relevance of the expression of the Interleukin-2-Receptor α subunit (IL2RA/CD25) as a biomarker of CML progression, suggesting its potential use as a therapeutic target for CAR-based therapies. Here we show the development of a CAR-NK therapy model able to target efficiently a blast crisis cell line (K562). The design of the CAR was based on the scFv of the clinically approved anti-CD25 monoclonal antibody (Basiliximab). The CAR construct was integrated into NK92 cells resulting in the generation of CD25 CAR-NK92 cells. Target K562 cells were engineered by lentiviral gene transfer of CD25. In vitro functionality experiments and in vivo leukemogenicity experiments in NSG mice transplanted by K562-CD25 cells showed the efficacy and specificity of this strategy. These proof-of-concept studies could represent a first step for further development of this technology in refractory/relapsed (R/R) CML patients in BP as well as in R/R acute myeloblastic leukemias (AML).

Report this publication

Statistics

Seen <100 times