Translational strategy to support the first-in-human study of a TCR-like T cell bispecific with an in vitro-based safety approach
results in skin co-culture models, were hypothesized to be driven by the target-independent activation capability of the UCHT1-based CD3 binder, potentially enhanced in patients with a systemic pro-inflammatory profile. This study provides a translational framework for TCR-based immunotherapies, demonstrating the successful application of NAMs to define a safe starting dose while highlighting the critical need for refining these methodologies to accurately predict complex, systemic immune-related adverse events, particularly those involving barrier organs.
Authors
- Tina Weinzierl
- Angélique Augustin
- Karen Dernick
- Olaf Broders
- Blandine Avignon
- Daniela Ortiz Franyuti (ORCID: https://orcid.org/0000-0002-8783-1960)
- Christine Zihlmann
- Giulia Raggi
- Miro J. Eigenmann (ORCID: https://orcid.org/0000-0002-7193-9264)
- Anna Maria Giusti (ORCID: https://orcid.org/0000-0002-5694-3732)
- Estelle Marrer‐Berger (ORCID: https://orcid.org/0000-0002-9677-0549)
- N Hobi
- Evelyne Durr
- Ramona Matheis
- S Fischer
- Elisabeth Husar (ORCID: https://orcid.org/0000-0002-8273-9874)
- Nino Keshelava (ORCID: https://orcid.org/0009-0001-0978-3393)
- Fabian Häusermann
- Céline Marban-Doran
- Nick Flinn
- Andreas Roller (ORCID: https://orcid.org/0000-0001-6335-0962)
- Lauriane Cabon (ORCID: https://orcid.org/0000-0001-8472-2227)
- Christophe Boetsch (ORCID: https://orcid.org/0009-0005-8467-0339)
- Virginie Micallef
- Nadine Stokar‐Regenscheit (ORCID: https://orcid.org/0000-0003-4089-2026)
- Vincent Wolowski
- Antje‐Christine Walz (ORCID: https://orcid.org/0000-0002-2177-545X)
- Régine Gérard
- Ekaterina Breous-Nystrom
- Liudmila Polonchuk (ORCID: https://orcid.org/0000-0002-6947-2845)
- Iris Martinez Quetglas (ORCID: https://orcid.org/0009-0009-9558-1517)
- Laurent Juglair
- H. Grote
- Pamela Ruffiner
- Tulun Saylan
- Satyajit Shetage
- Desirée Schubert
- Salma Sadok
- Nikolche Gjorevski
- Nathalie Schaub
- Stefan Kustermann
- Simon Patrick Keiser
Institutions
- Roche (Switzerland) (CH)
- Roche (China) (CN)
- Swisscom (Switzerland) (CH)
Publication Details
- Journal
- Frontiers in Immunology
- Published
- 2026-04-17
- DOI
- https://doi.org/10.3389/fimmu.2026.1736584
- Primary Topic
- CAR-T cell therapy research
- Type
- article
- Field-Weighted Citation Impact
- 0.00