Your browser doesn't support javascript.
loading
An anti-CD19/CTLA-4 switch improves efficacy and selectivity of CAR T cells targeting CD80/86-upregulated DLBCL.
Prinz, Lars Fabian; Riet, Tobias; Neureuther, Daniel Felix; Lennartz, Simon; Chrobok, Danuta; Hübbe, Hanna; Uhl, Gregor; Riet, Nicole; Hofmann, Petra; Hösel, Marianna; Simon, Adrian Georg; Tetenborg, Luis; Segbers, Paul; Shimono, Joji; Gödel, Philipp; Balke-Want, Hyatt; Flümann, Ruth; Knittel, Gero; Reinhardt, Hans Christian; Scheid, Christoph; Büttner, Reinhard; Chapuy, Björn; Ullrich, Roland Tillmann; Hallek, Michael; Chmielewski, Markus Martin.
Afiliación
  • Prinz LF; Department I of Internal Medicine, University Hospital Cologne, 50937 Cologne, Germany; Center for Molecular Medicine Cologne (CMMC), 50931 Cologne, Germany. Electronic address: lars.prinz1@uk-koeln.de.
  • Riet T; Department I of Internal Medicine, University Hospital Cologne, 50937 Cologne, Germany; Center for Molecular Medicine Cologne (CMMC), 50931 Cologne, Germany.
  • Neureuther DF; Department I of Internal Medicine, University Hospital Cologne, 50937 Cologne, Germany; Center for Molecular Medicine Cologne (CMMC), 50931 Cologne, Germany.
  • Lennartz S; Department I of Internal Medicine, University Hospital Cologne, 50937 Cologne, Germany; Center for Molecular Medicine Cologne (CMMC), 50931 Cologne, Germany.
  • Chrobok D; Department I of Internal Medicine, University Hospital Cologne, 50937 Cologne, Germany; Center for Molecular Medicine Cologne (CMMC), 50931 Cologne, Germany.
  • Hübbe H; Heidelberg University, 69117 Heidelberg, Germany.
  • Uhl G; Department I of Internal Medicine, University Hospital Cologne, 50937 Cologne, Germany; Center for Molecular Medicine Cologne (CMMC), 50931 Cologne, Germany.
  • Riet N; Center for Molecular Medicine Cologne (CMMC), 50931 Cologne, Germany.
  • Hofmann P; Department I of Internal Medicine, University Hospital Cologne, 50937 Cologne, Germany; Center for Molecular Medicine Cologne (CMMC), 50931 Cologne, Germany.
  • Hösel M; Department I of Internal Medicine, University Hospital Cologne, 50937 Cologne, Germany.
  • Simon AG; Institute of Pathology, University Hospital Cologne, 50937 Cologne, Germany.
  • Tetenborg L; Department I of Internal Medicine, University Hospital Cologne, 50937 Cologne, Germany; Center for Molecular Medicine Cologne (CMMC), 50931 Cologne, Germany.
  • Segbers P; Department I of Internal Medicine, University Hospital Cologne, 50937 Cologne, Germany; Center for Molecular Medicine Cologne (CMMC), 50931 Cologne, Germany.
  • Shimono J; Department of Hematology, Oncology and Tumorimmunology, Charité University Medical Center Berlin, Benjamin Franklin Campus, 12203 Berlin, Germany.
  • Gödel P; Department I of Internal Medicine, University Hospital Cologne, 50937 Cologne, Germany.
  • Balke-Want H; Department I of Internal Medicine, University Hospital Cologne, 50937 Cologne, Germany; Stanford Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University, Stanford, CA, USA.
  • Flümann R; Department I of Internal Medicine, University Hospital Cologne, 50937 Cologne, Germany; Center for Molecular Medicine Cologne (CMMC), 50931 Cologne, Germany; Cologne Excellence Cluster on Cellular Stress Response in Aging-Associated Diseases (CECAD), University of Cologne, 50931 Cologne, Germany; Mi
  • Knittel G; University Hospital Essen, Department of Hematology and Stem Cell Transplantation, West German Cancer Center, German Cancer Consortium Partner Site Essen, Center for Molecular Biotechnology, Hufelandstr. 55, 45147 Essen, Germany.
  • Reinhardt HC; University Hospital Essen, Department of Hematology and Stem Cell Transplantation, West German Cancer Center, German Cancer Consortium Partner Site Essen, Center for Molecular Biotechnology, Hufelandstr. 55, 45147 Essen, Germany.
  • Scheid C; Department I of Internal Medicine, University Hospital Cologne, 50937 Cologne, Germany.
  • Büttner R; Institute of Pathology, University Hospital Cologne, 50937 Cologne, Germany.
  • Chapuy B; Department of Hematology, Oncology and Tumorimmunology, Charité University Medical Center Berlin, Benjamin Franklin Campus, 12203 Berlin, Germany.
  • Ullrich RT; Department I of Internal Medicine, University Hospital Cologne, 50937 Cologne, Germany; Center for Molecular Medicine Cologne (CMMC), 50931 Cologne, Germany.
  • Hallek M; Department I of Internal Medicine, University Hospital Cologne, 50937 Cologne, Germany.
  • Chmielewski MM; Department I of Internal Medicine, University Hospital Cologne, 50937 Cologne, Germany; Center for Molecular Medicine Cologne (CMMC), 50931 Cologne, Germany. Electronic address: markus.chmielewski@uk-koeln.de.
Cell Rep Med ; 5(2): 101421, 2024 Feb 20.
Article en En | MEDLINE | ID: mdl-38340727
ABSTRACT
Chimeric antigen receptor T cell (CAR T) therapy is a potent treatment for relapsed/refractory (r/r) B cell lymphomas but provides lasting remissions in only ∼40% of patients and is associated with serious adverse events. We identify an upregulation of CD80 and/or CD86 in tumor tissue of (r/r) diffuse large B cell lymphoma (DLBCL) patients treated with tisagenlecleucel. This finding leads to the development of the CAR/CCR (chimeric checkpoint receptor) design, which consists of a CD19-specific first-generation CAR co-expressed with a recombinant CTLA-4-linked receptor with a 4-1BB co-stimulatory domain. CAR/CCR T cells demonstrate superior efficacy in xenograft mouse models compared with CAR T cells, superior long-term activity, and superior selectivity in in vitro assays with non-malignant CD19+ cells. In addition, immunocompetent mice show an intact CD80-CD19+ B cell population after CAR/CCR T cell treatment. The results reveal the CAR/CCR design as a promising strategy for further translational study.
Asunto(s)
Palabras clave
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Linfocitos T / Linfoma de Células B Grandes Difuso Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Cell Rep Med Año: 2024 Tipo del documento: Article
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Linfocitos T / Linfoma de Células B Grandes Difuso Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Cell Rep Med Año: 2024 Tipo del documento: Article