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

Authors
  • Mookerjee, Ananda
  • Graciotti, Michele1
  • Kandalaft, Lana E.1
  • 1 Department of Oncology, University Hospital of Lausanne, Lausanne 1011, Switzerland
Type
Published Article
Journal
Cancers
Publisher
MDPI AG
Publication Date
Jan 04, 2019
Volume
11
Issue
1
Identifiers
DOI: 10.3390/cancers11010040
PMID: 30621204
PMCID: PMC6356194
Source
PubMed Central
Keywords
License
Green

Abstract

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.

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