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

个性化癌症疫苗策略可诱导多功能T细胞,并在卵巢癌中展现出临床疗效

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作者: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 Jr ,George Coukos ,Alexandre Harari ,Lana E Kandalaft

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.

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