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TCR/CD3-based synthetic antigen receptors (TCC) convey superior antigen sensitivity combined with high fidelity of activation.
Mühlgrabner, Vanessa; Peters, Timo; Velasco Cárdenas, Rubí M-H; Salzer, Benjamin; Göhring, Janett; Plach, Angelika; Höhrhan, Maria; Perez, Iago Doel; Goncalves, Vasco Dos Reis; Farfán, Jesús Siller; Lehner, Manfred; Stockinger, Hannes; Schamel, Wolfgang W; Schober, Kilian; Busch, Dirk H; Hudecek, Michael; Dushek, Omer; Minguet, Susana; Platzer, René; Huppa, Johannes B.
Afiliación
  • Mühlgrabner V; Medical University of Vienna, Center for Pathophysiology, Infectiology and Immunology, Institute for Hygiene and Applied Immunology, Vienna, Austria.
  • Peters T; Medical University of Vienna, Center for Pathophysiology, Infectiology and Immunology, Institute for Hygiene and Applied Immunology, Vienna, Austria.
  • Velasco Cárdenas RM; Department of Immunology, Faculty of Biology, University of Freiburg, Germany.
  • Salzer B; Center for Biological Signaling Studies (BIOSS), University of Freiburg, Germany.
  • Göhring J; Center for Integrative Biological Signaling Studies (CIBSS), University of Freiburg, Germany.
  • Plach A; St. Anna Children's Cancer Research Institute (CCRI), 1090, Vienna, Austria.
  • Höhrhan M; Christian Doppler Laboratory for Next Generation CAR T Cells, 1090, Vienna, Austria.
  • Perez ID; Medical University of Vienna, Center for Pathophysiology, Infectiology and Immunology, Institute for Hygiene and Applied Immunology, Vienna, Austria.
  • Goncalves VDR; Medical University of Vienna, Center for Pathophysiology, Infectiology and Immunology, Institute for Hygiene and Applied Immunology, Vienna, Austria.
  • Farfán JS; Medical University of Vienna, Center for Pathophysiology, Infectiology and Immunology, Institute for Hygiene and Applied Immunology, Vienna, Austria.
  • Lehner M; Medical University of Vienna, Center for Pathophysiology, Infectiology and Immunology, Institute for Hygiene and Applied Immunology, Vienna, Austria.
  • Stockinger H; Medizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg, Würzburg, Germany.
  • Schamel WW; Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford, UK.
  • Schober K; St. Anna Children's Cancer Research Institute (CCRI), 1090, Vienna, Austria.
  • Busch DH; Christian Doppler Laboratory for Next Generation CAR T Cells, 1090, Vienna, Austria.
  • Hudecek M; Medical University of Vienna, Center for Pathophysiology, Infectiology and Immunology, Institute for Hygiene and Applied Immunology, Vienna, Austria.
  • Dushek O; Department of Immunology, Faculty of Biology, University of Freiburg, Germany.
  • Minguet S; Center for Biological Signaling Studies (BIOSS), University of Freiburg, Germany.
  • Platzer R; Center for Integrative Biological Signaling Studies (CIBSS), University of Freiburg, Germany.
  • Huppa JB; Mikrobiologisches Institut-Klinische Mikrobiologie, Immunologie und Hygiene, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.
Sci Adv ; 10(36): eadj4632, 2024 Sep 06.
Article en En | MEDLINE | ID: mdl-39231214
ABSTRACT
Low antigen sensitivity and a gradual loss of effector functions limit the clinical applicability of chimeric antigen receptor (CAR)-modified T cells and call for alternative antigen receptor designs for effective T cell-based cancer immunotherapy. Here, we applied advanced microscopy to demonstrate that TCR/CD3-based synthetic constructs (TCC) outperform second-generation CAR formats with regard to conveyed antigen sensitivities by up to a thousandfold. TCC-based antigen recognition occurred without adverse nonspecific signaling, which is typically observed in CAR-T cells, and did not depend-unlike sensitized peptide/MHC detection by conventional T cells-on CD4 or CD8 coreceptor engagement. TCC-endowed signaling properties may prove critical when targeting antigens in low abundance and aiming for a durable anticancer response.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Receptores de Antígenos de Linfocitos T / Receptores Quiméricos de Antígenos Límite: Humans Idioma: En Revista: Sci Adv Año: 2024 Tipo del documento: Article País de afiliación: Austria Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Receptores de Antígenos de Linfocitos T / Receptores Quiméricos de Antígenos Límite: Humans Idioma: En Revista: Sci Adv Año: 2024 Tipo del documento: Article País de afiliación: Austria Pais de publicación: Estados Unidos