Replication-Competent, Tumor-Specific Immuno-Gene Vectors Allow for Exchange of Transgenes and Lead to Viral Persistence Following IV Administration
Armed T-SIGn vectors exhibit the same high tumor selectivity and replicative activity as the unarmed parent EnAd and achieve consistent viral delivery to a broad range of epithelial tumor tissues. The aggregated safety analysis revealed that safety and tolerability are defined by systemic viremia but not off-target or transgene-related toxicities. Nucleic acid and cytokine release from tumors and changes in the TME (e.g., CD8+ T cells), indicative of the mechanism of action of replication-competent viral vectors, constitute potentially valuable data to support the definition of a recommended phase 2 dose and the assessment of the benefit of multicycle administration.
Authors
- Aung Naing (ORCID: https://orcid.org/0000-0002-4803-8513)
- Séan M. O’Cathail (ORCID: https://orcid.org/0000-0001-5574-9199)
- M. Hawkins (ORCID: https://orcid.org/0000-0002-6669-0628)
- Andrea Stacey
- Lee S. Rosen (ORCID: https://orcid.org/0000-0003-2503-6133)
- Guru Sonpavde (ORCID: https://orcid.org/0000-0002-1010-9611)
- Rui-Ru Ji
- Maria Stella Sasso
- Christian H. Ottensmeier (ORCID: https://orcid.org/0000-0003-3619-1657)
- Eileen E. Parkes (ORCID: https://orcid.org/0000-0002-7855-3698)
- Brian Andrew Van Tine
- Matthew C. Thomas
- Oliver Rosen (ORCID: https://orcid.org/0000-0002-4968-3143)
Institutions
- Biogen (United States) (US)
- The University of Texas MD Anderson Cancer Center (US)
- Washington University in St. Louis (US)
- Churchill Hospital (GB)
- Clatterbridge Cancer Centre NHS Foundation Trust (GB)
- Florida Hospital Cancer Institute (US)
- Oxford Biotherapeutics (United Kingdom) (GB)
- Sarcoma Oncology Center (US)
- The London College (GB)
- University College London (GB)
- University of Glasgow (GB)
Publication Details
- Journal
- Journal of Immunotherapy and Precision Oncology
- Published
- 2025-11-25
- DOI
- https://doi.org/10.36401/jipo-25-18
- Citations
- 1
- Primary Topic
- Virus-based gene therapy research
- Type
- article
- Field-Weighted Citation Impact
- 1.82
Funders
- Bristol-Myers Squibb
- Eli Lilly and Company
- Pfizer
- Gilead Sciences
- American Society of Clinical Oncology
- Karyopharm Therapeutics
- Regeneron Pharmaceuticals
- Wellcome Trust
- Exelixis
- Society for Immunotherapy of Cancer
- Cytokinetics
- Millendo Therapeutics
- Deciphera Pharmaceuticals
- Incyte
- Calithera Biosciences
- NGM Biopharmaceuticals
- Seagen
- Natera
- Cancer Research UK
- National Institute for Health and Care Research
- University College London
- University of Oxford
- Daiichi-Sankyo
- Astellas Pharma
- European Society for Medical Oncology
- University College London Hospitals NHS Foundation Trust
- STCube
- Servier
- Mereo BioPharma
- EMD Serono
- Loxo Oncology
- National Cancer Institute
- Janssen Biotech
- Daiichi Sankyo Europe