Personalized cancer vaccine strategy elicits polyfunctional T cells and demonstrates clinical benefits in ovarian cancer
János L. Tanyi, Cheryl Lai-Lai Chiang, Johanna Chiffelle, Anne‐Christine Thierry, Petra Baumgartener, Florian Huber, Christine Goepfert, David Tarussio, Stephanie Tissot, Drew A. Torigian, Harvey Nisenbaum, Brian J. Stevenson, Hajer Fritah Guiren, Ritaparna Ahmed, Anne-Laure Huguenin-Bergenat, Emese Zsíros, Michal Bassani‐Sternberg, Rosemarie Mick, Daniel J. Powell, George Coukos, Alexandre Harari, Lana E. Kandalaft
Abstract
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.