Intradermal DNA vaccination combined with dual CTLA-4 and PD-1 blockade provides robust tumor immunity in murine melanoma.
Animals
CD8-Positive T-Lymphocytes
/ drug effects
CTLA-4 Antigen
/ antagonists & inhibitors
Cancer Vaccines
/ immunology
Cell Line, Tumor
Combined Modality Therapy
Humans
Immunotherapy
Melanoma, Experimental
/ immunology
Mice
Programmed Cell Death 1 Receptor
/ antagonists & inhibitors
Vaccination
Vaccines, DNA
/ immunology
Journal
PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081
Informations de publication
Date de publication:
2019
2019
Historique:
received:
20
11
2018
accepted:
19
05
2019
entrez:
1
6
2019
pubmed:
1
6
2019
medline:
6
2
2020
Statut:
epublish
Résumé
We aimed to explore whether the combination of intradermal DNA vaccination, to boost immune response against melanoma antigens, and immune checkpoint blockade, to alleviate immunosuppression, improves antitumor effectiveness in a murine B16F10 melanoma tumor model. Compared to single treatments, a combination of intradermal DNA vaccination (ovalbumin or gp100 plasmid adjuvanted with IL12 plasmid) and immune checkpoint CTLA-4/PD-1 blockade resulted in a significant delay in tumor growth and prolonged survival of treated mice. Strong activation of the immune response induced by combined treatment resulted in a significant antigen-specific immune response, with elevated production of antigen-specific IgG antibodies and increased intratumoral CD8+ infiltration. These results indicate a potential application of the combined DNA vaccination and immune checkpoint blockade, specifically, to enhance the efficacy of DNA vaccines and to overcome the resistance to immune checkpoint inhibitors in certain cancer types.
Identifiants
pubmed: 31150505
doi: 10.1371/journal.pone.0217762
pii: PONE-D-18-33350
pmc: PMC6544376
doi:
Substances chimiques
CTLA-4 Antigen
0
Cancer Vaccines
0
Pdcd1 protein, mouse
0
Programmed Cell Death 1 Receptor
0
Vaccines, DNA
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0217762Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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