Authors: Tanyi, Janos L.; Chiang, Cheryl L.-L.; Chiffelle, Johanna; Thierry, Anne-Christine; Baumgartener, Petra; Huber, Florian; Goepfert, 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; Harari, Alexandre; Kandalaft, Lana E.
Online: https://www.nature.com/articles/s41541-021-00297-5
Issue: NPJ Vaccines . 2021 Mar 15;6(1):36.
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.
