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

Mühlgrabner V, Peters T, Velasco Cárdenas RM, Salzer B, Göhring J, Plach A, Höhrhan M, Perez ID, Reis Goncalves VD, Farfán JS, Lehner M, Stockinger H, Schamel WW, Schober K, Busch DH, Hudecek M, Dushek O, Minguet S, Platzer R, Huppa JB (2024)

Publication Type: Journal article

Publication year: 2024

Journal

Science Advances American Association for the Advancement of Science

Book Volume: 10

Article Number: eadj4632

Journal Issue: 36

DOI: 10.1126/sciadv.adj4632

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.

Authors with CRIS profile

Kilian Schober Institute of Microbiology – Clinical Microbiology, Immunology and Hygiene

Involved external institutions

Medizinische Universität Wien AT Austria (AT) Albert-Ludwigs-Universität Freiburg DE Germany (DE) St. Anna Kinderkrebsforschung AT Austria (AT) Universitätsklinikum Würzburg DE Germany (DE) University of Oxford GB United Kingdom (GB) Technische Universität München (TUM) DE Germany (DE)

How to cite

APA:

Mühlgrabner, V., Peters, T., Velasco Cárdenas, R.M., Salzer, B., Göhring, J., Plach, A.,... Huppa, J.B. (2024). TCR/CD3-based synthetic antigen receptors (TCC) convey superior antigen sensitivity combined with high fidelity of activation. Science Advances, 10(36). https://doi.org/10.1126/sciadv.adj4632

MLA:

Mühlgrabner, Vanessa, et al. "TCR/CD3-based synthetic antigen receptors (TCC) convey superior antigen sensitivity combined with high fidelity of activation." Science Advances 10.36 (2024).

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