期刊
NPJ VACCINES
卷 6, 期 1, 页码 -出版社
NATURE RESEARCH
DOI: 10.1038/s41541-021-00297-5
关键词
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资金
- National Cancer Institute [P01-CA83638]
- Immunotherapy Initiative for Ovarian Cancer (ITI-OC)
- Markus Foundation
- Rivkin Center for Ovarian Cancer
- Ludwig Institute for Cancer Research
- Research Foundation for the Treatment of Ovarian Cancer, Inc.
By adding ASA and low-dose IL-2 to the OCDC-Bev-Cy combination regimen, we elicited vaccine-specific T-cell responses that positively correlated with prolonged time-to-progression and overall survival in patients. This combinatorial strategy was effective and demonstrated the utility of the ID8 ovarian model for future ovarian trial development.
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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