A prime/boost vaccine platform efficiently identifies CD27 agonism and depletion of myeloid-derived suppressor cells as therapies that rationally combine with checkpoint blockade in ovarian cancer.

Autor: McGray AJR; Center for Immunotherapy, Roswell Park Comprehensive Cancer Center, Roswell Park Cancer Institute, Elm and Carlton Sts, Buffalo, NY, 14263, USA. ajrobert.mcgray@roswellpark.org., Eppolito C; Center for Immunotherapy, Roswell Park Comprehensive Cancer Center, Roswell Park Cancer Institute, Elm and Carlton Sts, Buffalo, NY, 14263, USA., Miliotto A; Center for Immunotherapy, Roswell Park Comprehensive Cancer Center, Roswell Park Cancer Institute, Elm and Carlton Sts, Buffalo, NY, 14263, USA., Singel KL; Department of Immunology, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA.; Office of Evaluation, Performance, and Reporting, National Institutes of Health, Bethesda, MD, USA., Stephenson K; McMaster Immunology Research Centre, McMaster University, Hamilton, ON, Canada.; Turnstone Biologics, Ottawa, ON, Canada., Lugade A; Center for Immunotherapy, Roswell Park Comprehensive Cancer Center, Roswell Park Cancer Institute, Elm and Carlton Sts, Buffalo, NY, 14263, USA., Segal BH; Department of Immunology, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA.; Department of Internal Medicine, Roswell Park Comprehensive Cancer Center and Jacobs School of Medicine and Biomedical Sciences, University At Buffalo, Buffalo, NY, USA., Keler T; Celldex Therapeutics, Hampton, NJ, USA., Webster G; Innate Immunotherapeutics, Auckland, New Zealand., Lichty B; McMaster Immunology Research Centre, McMaster University, Hamilton, ON, Canada., Kozbor D; Department of Immunology, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA., Odunsi K; Center for Immunotherapy, Roswell Park Comprehensive Cancer Center, Roswell Park Cancer Institute, Elm and Carlton Sts, Buffalo, NY, 14263, USA. odunsia@bsd.uchicago.edu.; University of Chicago Comprehensive Cancer Center, 5841 South Maryland Avenue, MC1140, Chicago, IL, 60637, USA. odunsia@bsd.uchicago.edu.
Jazyk: angličtina
Zdroj: Cancer immunology, immunotherapy : CII [Cancer Immunol Immunother] 2021 Dec; Vol. 70 (12), pp. 3451-3460. Date of Electronic Publication: 2021 Apr 20.
DOI: 10.1007/s00262-021-02936-1
Abstrakt: Cancer immunotherapies have generated remarkable clinical responses for some patients with advanced/metastatic disease, prompting exploration of rational combination therapies to bolster anti-tumor immunity in patients with limited response or those who experience tumor progression following an initial response to immunotherapy. In contrast to other tumor indications, objective response rates to single-agent PD-1/PD-L1 blockade in ovarian cancer are limited, suggesting a need to identify combinatorial approaches that lead to tumor regression in a setting where checkpoint blockade alone is ineffective. Using a pre-clinical model of aggressive intraperitoneal ovarian cancer, we have previously reported on a heterologous prime/boost cancer vaccine that elicits robust anti-tumor immunity, prolongs survival of tumor-bearing mice, and which is further improved when combined with checkpoint blockade. As tumor control in this model is CD8 + T cell dependent, we reasoned that the prime/boost vaccine platform could be used to explore additional treatment combinations intended to bolster the effects of CD8 + T cells. Using whole tumor transcriptomic data, we identified candidate therapeutic targets anticipated to rationally combine with prime/boost vaccination. In the context of a highly effective cancer vaccine, CD27 agonism or antibody-mediated depletion of granulocytic cells each modestly increased tumor control following vaccination, with anti-PD-1 therapy further improving treatment efficacy. These findings support the use of immunotherapies with well-defined mechanisms(s) of action as a valuable platform for identifying candidate combination approaches for further therapeutic testing in ovarian cancer.
(© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
Databáze: MEDLINE
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