TCR/CD3-based synthetic antigen receptors (TCC) convey superior antigen sensitivity combined with high fidelity of activation

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

Object Details

• Location: Deutsche Nationalbibliothek Frankfurt am Main
• Extent: Online-Ressource
• Language: Englisch
• Notes: Science advances. - 10, 36 (2024) , eadj4632, ISSN: 2375-2548

Contributors, Places and Time

• Event: Veröffentlichung
• (where): Freiburg
• (who): Universität
• (when): 2025
• Creator: Mühlgrabner, Vanessa ; Peters, Timo ; Velasco Cárdenas, Rubí Misol-Há ; Salzer, Benjamin ; Göhring, Janett ; Plach, Angelika ; Höhrhan, Maria ; Perez, Iago Doel ; Goncalves, Vasco Dos Reis ; Farfán, Jesús Siller ; Lehner, Manfred ; Stockinger, Hannes ; Schamel, Wolfgang ; Schober, Kilian ; Busch, Dirk H. ; Hudecek, Michael ; Dushek, Omer ; Minguet, Susana ; Platzer, René ; Huppa, Johannes

Further information

• DOI: 10.1126/sciadv.adj4632
• URN: urn:nbn:de:bsz:25-freidok-2616474
• Rights: Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
• Last update: 16.04.2029, 3:37 AM CEST