Integrating binding affinity and tonic signaling enables a rational CAR design for augmented T cell function
Data emphasize that tonic signaling is not always due to the positive charge but can be driven by hydrophobic interactions of the scFv. CAR binding affinity above the threshold and tonic signaling are required for sustained T cell functionality in antigen rechallenge and long-term tumor control.
Authors
- Moritz Ertelt (ORCID: https://orcid.org/0009-0004-2506-6660)
- Vivian Haas (ORCID: https://orcid.org/0000-0002-7047-5517)
- Valerie Bezler (ORCID: https://orcid.org/0000-0003-0219-012X)
- Andreas Hombach (ORCID: https://orcid.org/0000-0001-9328-8442)
- Dennis Christoph Harrer (ORCID: https://orcid.org/0000-0001-7512-572X)
- Rasmus U. W. Friis
- Árpád Szöőr (ORCID: https://orcid.org/0000-0002-3727-6129)
- Markus Barden (ORCID: https://orcid.org/0000-0002-4923-2254)
- Clara T. Schoeder (ORCID: https://orcid.org/0000-0002-4664-961X)
- Lukáš Veľas
- Astrid Holzinger
- Bence Gergely (ORCID: https://orcid.org/0000-0001-9005-6910)
- Hinrich Abken (ORCID: https://orcid.org/0000-0002-4302-3240)
- György Vereb (ORCID: https://orcid.org/0000-0003-2157-3265)
- Philip Pervan
- Gerhard J. Schütz
- Patrick Ronan Elsenbroich
Institutions
- University of Debrecen (HU)
- TU Wien (AT)
- University of Cologne (DE)
- Leibniz Association (DE)
- Fraunhofer Institute for Cell Therapy and Immunology (DE)
- University Hospital Cologne (DE)
- Leibniz Institute for Immunotherapy
- Center for Scalable Data Analytics and Artificial Intelligence (DE)
- Leipzig University (DE)
- Technical University of Denmark (DK)
Publication Details
- Journal
- Journal for ImmunoTherapy of Cancer
- Published
- 2024-12-01
- DOI
- https://doi.org/10.1136/jitc-2024-010208
- Citations
- 12
- Primary Topic
- CAR-T cell therapy research
- Type
- article
- Field-Weighted Citation Impact
- 3.39
Funders
- Deutsche Forschungsgemeinschaft
- Bundesministerium für Bildung und Forschung
- Hungarian Scientific Research Fund
- Magyar Tudományos Akadémia
- Sächsisches Staatsministerium für Wissenschaft und Kunst
- Innovációs és Technológiai Minisztérium
- University of California, San Francisco
- National Research, Development and Innovation Office