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 · 2021 · npj Vaccines
Paper
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.
Analysis
This Phase I trial investigated an enhanced personalized whole-tumor lysate-pulsed dendritic cell vaccine (OCDC) regimen combined with bevacizumab (Bev), cyclophosphamide (Cy), acetylsalicylic acid (ASA), and low-dose interleukin-2 (IL-2) for recurrent advanced ovarian cancer.
Discovery
Vladimir Zyrin; Evgeniy Mozheiko; Ivan Valiev; Alexey Lazarev; Tigran Gevorkyan; Matvey Murashko; Konstantin Okonechnikov
Ashling Cannon
Dinghai Zheng; Justin Hong; Jun Wang; Adrien Villain; Mickaël Costallat; Fernando Ulloa Montoya; Vikram Agarwal
Petar Brlek; Jan Kolić; Luka Bulić; Vedrana Škaro; Dragan Primorac
Almohanad A. Alkayyal
Crodel CC; Gork L; Göpel W; Linke P; Sinn K; Miethke J; Hochhaus A; Hilgendorf I
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