Combination of immune checkpoint blockade with DNA cancer vaccine induces potent antitumor immunity against P815 mastocytoma

Autor: Sophie Lucas, Alessandra Lopes, Véronique Préat, Benoît Van den Eynde, Spela Kos, Didier Colau, Gaëlle Vandermeulen, Kevin Vanvarenberg
Přispěvatelé: UCL - SSS/LDRI - Louvain Drug Research Institute, UCL - SSS/DDUV/GECE - Génétique cellulaire
Rok vydání: 2018
Předmět:
0301 basic medicine
Granzyme B production
Potent Immune Response
T cell
Science
Programmed Cell Death 1 Receptor
chemical and pharmacologic phenomena
Cancer Vaccines
Article
P815 Mastocytoma
DNA vaccination
Mice
03 medical and health sciences
Cancer Vaccination
0302 clinical medicine
Immune system
Tumor Microenvironment
Vaccines
DNA
Animals
Medicine
Tumor Growth Delay
CTLA-4 Antigen
Neoplasm Metastasis
Tumor microenvironment
Multidisciplinary
biology
business.industry
Antibodies
Monoclonal
Mastocytoma
biochemical phenomena
metabolism
and nutrition
Immune checkpoint
Survival Rate
Treatment Outcome
030104 developmental biology
medicine.anatomical_structure
030220 oncology & carcinogenesis
Cancer research
biology.protein
Immunotherapy
Cancer vaccine
Antibody
Immune Checkpoint Blockers (ICBs)
business
Zdroj: Scientific Reports, Vol 8, Iss 1, Pp 1-11 (2018)
Scientific reports, Vol. 8, no.1, p. 15732 (2018)
Scientific Reports
DOI: 10.1038/s41598-018-33933-7
Popis: DNA vaccination against cancer has become a promising strategy for inducing a specific and long-lasting antitumor immunity. However, DNA vaccines fail to generate potent immune responses when used as a single therapy. To enhance their activity into the tumor, a DNA vaccine against murine P815 mastocytoma was combined with antibodies directed against the immune checkpoints CTLA4 and PD1. The combination of these two strategies delayed tumor growth and enhanced specific antitumor immune cell infiltration in comparison to the corresponding single therapies. The combination also promoted IFNg, IL12 and granzyme B production in the tumor microenvironment and decreased the formation of liver metastasis in a very early phase of tumor development, enabling 90% survival. These results underline the complementarity of DNA vaccination and immune checkpoint blockers in inducing a potent immune response, by exploiting the generation of antigen-specific T cells by the vaccine and the ability of immune checkpoint blockers to enhance T cell activity and infiltration in the tumor. These findings suggest how and why a rational combination therapy can overcome the limits of DNA vaccination but could also allow responses to immune checkpoint blockers in a larger proportion of subjects.
Databáze: OpenAIRE
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