NEO-STIM advances personalized neoantigen-specific adoptive T cell therapy
Neoantigen-based adoptive T cell therapies (ACTs) represent a promising avenue in cancer immunotherapy due to their exquisite tumor specificity. The first cell-based immunotherapy for a solid tumor, comprising tumor-infiltrating lymphocytes, recently received FDA approval. Building on this, we designed a distinct ACT approach, where T cell responses against personalized neoantigens are systematically generated from autologous peripheral blood. Here we report the establishment of NEO-STIM, an ex vivo induction process to prime and expand pre-existing memory and de novo CD8<sup>+</sup> and CD4<sup>+</sup> T cell responses, thereby highlighting critical parameters for generating potent neoantigen-specific T cell responses. The drug products comprise mutant-reactive, polyfunctional, and cytotoxic CD8<sup>+</sup> and CD4<sup>+</sup> T cells, able to recognize autologous tumor material. Following infusion, T cell responses are detected in tumor and blood of a patient, and display activated/exhausted and cytotoxic phenotypes. A first-in-human clinical trial (NCT04625205) recently further validated proof-of-concept, supporting continued development of this ACT approach.
Authors
- B. Nuijen
- Michael S. Rooney
- Michael S. Nelson (ORCID: https://orcid.org/0000-0003-0480-5597)
- N. M. Schumacher Ton
- Vikram R. Juneja (ORCID: https://orcid.org/0000-0001-6011-6417)
- Susan Hannes (ORCID: https://orcid.org/0000-0003-4437-8083)
- Joost H. van den Berg (ORCID: https://orcid.org/0000-0002-4928-8397)
- Mark DeMario
- Saskia Scheij (ORCID: https://orcid.org/0000-0003-4547-9492)
- Divya Lenkala (ORCID: https://orcid.org/0000-0002-1867-9563)
- Sebastian Hymson (ORCID: https://orcid.org/0009-0001-1823-9680)
- Asaf Poran (ORCID: https://orcid.org/0000-0001-9118-1051)
- Rhianne Voogd (ORCID: https://orcid.org/0009-0002-4293-5587)
- Flavian D. Brown
- Jessica Kohler (ORCID: https://orcid.org/0000-0002-6074-5595)
- Renate de Boer
- Shirisha Meda
- Maartje W. Rohaan (ORCID: https://orcid.org/0000-0003-1470-9427)
- Marit van Buuren
- Brenda Raud (ORCID: https://orcid.org/0000-0002-1416-0529)
- Christina M. Arieta
- Ekaterina Esaulova (ORCID: https://orcid.org/0000-0001-9806-662X)
- Kristen N. Balogh (ORCID: https://orcid.org/0000-0002-8746-745X)
- N. Bakker
- Jesse Z. Dong (ORCID: https://orcid.org/0000-0002-4877-852X)
- Claudia Gottstein (ORCID: https://orcid.org/0009-0008-1117-8417)
- Maaike van Zon
- Richard B. Gaynor
- Kelledy Manson
- Kai Stewart
- John Srouji
- Joong Hyuk F. Sheen
- John B. Haanen
- Ziyan Xu
- Jessica S. W. Borgers
- John Attanasio
- Emily K. Jackson
- Brian McCarthy
Institutions
- Biogen (United States) (US)
- Johnson & Johnson (United States) (US)
- University of Pittsburgh (US)
- The Netherlands Cancer Institute (NL)
- Sanquin (NL)
- Yale University (US)
- Q Therapeutics (United States) (US)
- Springhouse (US)
- Oncode Institute (NL)
- AstraZeneca (Netherlands) (NL)
- BioNTech (Germany) (DE)
- Galapagos (Netherlands) (NL)
- BioNTech (United States) (US)
- University of Colorado Anschutz Medical Campus (US)
Publication Details
- Journal
- Nature Communications
- Published
- 2026-02-05
- DOI
- https://doi.org/10.1038/s41467-026-68680-1
- Primary Topic
- CAR-T cell therapy research
- Type
- article
- Field-Weighted Citation Impact
- 0.00