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Article

IL-15 and a Two-Step Maturation Process Improve Bone Marrow-Derived Dendritic Cell Cancer Vaccine

by 1,†,‡, 2,3,‡ and 1,2,3,*
1
Ovarian Cancer Research Center, University of Pennsylvania, Philadelphia, PA 19104, USA
2
Ludwig Cancer Research Center, University of Lausanne, Épalinges 1066, Switzerland
3
Department of Oncology, University Hospital of Lausanne, Lausanne 1011, Switzerland
*
Author to whom correspondence should be addressed.
Currently at: Cardiovascular Research Center, Icahn School of Medicine, Mount Sinai, New York, NY 10029, USA.
These authors contributed equally to this work.
Received: 27 November 2018 / Revised: 20 December 2018 / Accepted: 21 December 2018 / Published: 4 January 2019
(This article belongs to the Special Issue Cancer Vaccines: Research and Applications)
In the last 20 years, dendritic cells (DCs) have been largely used as a platform for therapeutic vaccination in cancer patients. However, despite its proven safety and ability to induce cancer specific immune responses, the clinical benefits of DC-based immunotherapy are currently very limited. Thus, novel approaches are still needed to boost its efficacy. Our group recently showed that squaric acid treatment of antigens is an important adjuvant that can increase vaccine-induced downstream immune responses and therapeutic outcomes. Here we further improved this dendritic cell vaccine formulation by developing a new method for differentiating and maturing DCs from their bone marrow precursors. Our data demonstrate that bone marrow-derived DCs differentiated with GM-CSF and IL-15 and matured with a maturation cocktail in two steps present a more mature and immunogenic phenotype, compared to standard DC preparations. Further suppression of the prostaglandin E2 pathway achieved even more immunogenic DC phenotypes. This vaccine was more potent at delaying tumor growth, improved animal survival and induced a more immunogenic and Th1-skewed T cell response in an ovarian cancer mouse model. These promising results support future efforts for the clinical translation of this approach. View Full-Text
Keywords: cancer vaccine; dendritic cell; ovarian cancer; interleukin 15; squaric acid cancer vaccine; dendritic cell; ovarian cancer; interleukin 15; squaric acid
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MDPI and ACS Style

Mookerjee, A.; Graciotti, M.; Kandalaft, L.E. IL-15 and a Two-Step Maturation Process Improve Bone Marrow-Derived Dendritic Cell Cancer Vaccine. Cancers 2019, 11, 40. https://0-doi-org.brum.beds.ac.uk/10.3390/cancers11010040

AMA Style

Mookerjee A, Graciotti M, Kandalaft LE. IL-15 and a Two-Step Maturation Process Improve Bone Marrow-Derived Dendritic Cell Cancer Vaccine. Cancers. 2019; 11(1):40. https://0-doi-org.brum.beds.ac.uk/10.3390/cancers11010040

Chicago/Turabian Style

Mookerjee, Ananda, Michele Graciotti, and Lana E. Kandalaft 2019. "IL-15 and a Two-Step Maturation Process Improve Bone Marrow-Derived Dendritic Cell Cancer Vaccine" Cancers 11, no. 1: 40. https://0-doi-org.brum.beds.ac.uk/10.3390/cancers11010040

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