Tanyi, Janos L; Chiang, Cheryl L-L; Chiffelle, Johanna; Thierry, Anne-Christine; Baumgartener, Petra; Huber, Florian; Göpfert, Christine; Tarussio, David; Tissot, Stephanie; Torigian, Drew A; Nisenbaum, Harvey L; Stevenson, Brian J; Guiren, Hajer Fritah; Ahmed, Ritaparna; Huguenin-Bergenat, Anne-Laure; Zsiros, Emese; Bassani-Sternberg, Michal; Mick, Rosemarie; Powell, Daniel J; Coukos, George; ... (2021). Personalized cancer vaccine strategy elicits polyfunctional T cells and demonstrates clinical benefits in ovarian cancer. NPJ vaccines, 6(1), p. 36. Springer Nature 10.1038/s41541-021-00297-5
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T cells are important for controlling ovarian cancer (OC). We previously demonstrated that combinatorial use of a personalized whole-tumor lysate-pulsed dendritic cell vaccine (OCDC), bevacizumab (Bev), and cyclophosphamide (Cy) elicited neoantigen-specific T cells and prolonged OC survival. Here, we hypothesize that adding acetylsalicylic acid (ASA) and low-dose interleukin (IL)-2 would increase the vaccine efficacy in a recurrent advanced OC phase I trial (NCT01132014). By adding ASA and low-dose IL-2 to the OCDC-Bev-Cy combinatorial regimen, we elicited vaccine-specific T-cell responses that positively correlated with patients' prolonged time-to-progression and overall survival. In the ID8 ovarian model, animals receiving the same regimen showed prolonged survival, increased tumor-infiltrating perforin-producing T cells, increased neoantigen-specific CD8+ T cells, and reduced endothelial Fas ligand expression and tumor-infiltrating T-regulatory cells. This combinatorial strategy was efficacious and also highlighted the predictive value of the ID8 model for future ovarian trial development.
Item Type: |
Journal Article (Original Article) |
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Division/Institute: |
05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP) > Institute of Animal Pathology |
UniBE Contributor: |
Göpfert, Christine |
Subjects: |
600 Technology > 630 Agriculture 600 Technology > 610 Medicine & health |
ISSN: |
2059-0105 |
Publisher: |
Springer Nature |
Language: |
English |
Submitter: |
Pamela Schumacher |
Date Deposited: |
10 Aug 2021 08:28 |
Last Modified: |
05 Dec 2022 15:52 |
Publisher DOI: |
10.1038/s41541-021-00297-5 |
Related URLs: |
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PubMed ID: |
33723260 |
BORIS DOI: |
10.48350/157773 |
URI: |
https://boris.unibe.ch/id/eprint/157773 |
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