Personalized cancer vaccine strategy elicits polyfunctional T cells and demonstrates clinical benefits in ovarian cancer.
Janos L TanyiCheryl Lai-Lai ChiangJohanna ChiffelleAnne-Christine ThierryPetra BaumgartenerFlorian HuberChristine GoepfertDavid TarussioStephanie TissotDrew A TorigianHarvey L NisenbaumBrian J StevensonHajer Fritah GuirenRitaparna AhmedAnne-Laure Huguenin-BergenatEmese ZsirosMichal Bassani-SternbergRosemarie MickDaniel J PowellGeorge CoukosAlexandre HarariLana Elias KandalaftPublished in: NPJ vaccines (2021)
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.
Keyphrases
- low dose
- high dose
- dendritic cells
- end stage renal disease
- induced apoptosis
- study protocol
- clinical trial
- newly diagnosed
- ejection fraction
- poor prognosis
- phase ii
- endothelial cells
- chronic kidney disease
- regulatory t cells
- cell cycle arrest
- randomized controlled trial
- peritoneal dialysis
- papillary thyroid
- prognostic factors
- transcription factor
- squamous cell carcinoma
- long non coding rna
- current status
- oxidative stress
- endoplasmic reticulum stress
- binding protein