Personalized cancer vaccine strategy elicits polyfunctional T cells and demonstrates clinical benefits in ovarian cancer

• Main Authors: Janos L. Tanyi, Cheryl L.-L. Chiang, Johanna Chiffelle, Anne-Christine Thierry, Petra Baumgartener, Florian Huber, Christine Goepfert, David Tarussio, Stephanie Tissot, Drew A. Torigian, Harvey L. Nisenbaum, Brian J. Stevenson, Hajer Fritah Guiren, Ritaparna Ahmed, Anne-Laure Huguenin-Bergenat, Emese Zsiros, Michal Bassani-Sternberg, Rosemarie Mick, Daniel J. Powell, George Coukos, Alexandre Harari, Lana E. Kandalaft
• Format: Article
• Language: English
• Published: Nature Publishing Group 2021-03-01
• Series: npj Vaccines
• Online Access: https://doi.org/10.1038/s41541-021-00297-5
• ISSN: 2059-0105

Abstract 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.