TLR-3 stimulation improves anti-tumor immunity elicited by dendritic cell exosome-based vaccines in a murine model of melanoma

Martina Damo, David S. Wilson, Eleonora Simeoni, Jeffrey A. Hubbell

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

Dendritic cell (DC)-derived exosomes (Dexo) contain the machinery necessary to activate potent antigen-specific immune responses. As promising cell-free immunogens, Dexo have been tested in previous clinical trials for cancer vaccine immunotherapy, yet resulted in limited therapeutic benefit. Here, we explore a novel Dexo vaccine formulation composed of Dexo purified from DCs loaded with antigens and matured with either the TLR-3 ligand poly(I:C), the TLR-4 ligand LPS or the TLR-9 ligand CpG-B. When poly(I:C) was used to produce exosomes together with ovalbumin (OVA), the resulting Dexo vaccine strongly stimulated OVA-specific CD8+ and CD4+ T cells to proliferate and acquire effector functions. When a B16F10 melanoma cell lysate was used to load DCs with tumor antigens during exosome production together with poly(I:C), we obtained a Dexo vaccine capable of inducing robust activation of melanoma-specific CD8+ T cells and the recruitment of cytotoxic CD8+ T cells, NK and NK-T cells to the tumor site, resulting in significantly reduced tumor growth and enhanced survival as compared to a Dexo vaccine formulation similar to the one previously tested on human patients. Our results indicate that poly(I:C) is a particularly favorable TLR agonist for DC maturation during antigen loading and exosome production for cancer immunotherapy.

Original languageEnglish (US)
Article number17622
JournalScientific Reports
Volume5
DOIs
StatePublished - Dec 3 2015
Externally publishedYes

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Exosomes
Dendritic Cells
Immunity
Melanoma
Vaccines
Neoplasms
T-Lymphocytes
Ovalbumin
Ligands
Immunotherapy
Antigens
Cancer Vaccines
Histocompatibility Antigens Class II
Neoplasm Antigens
Natural Killer Cells
Clinical Trials

ASJC Scopus subject areas

  • General

Cite this

TLR-3 stimulation improves anti-tumor immunity elicited by dendritic cell exosome-based vaccines in a murine model of melanoma. / Damo, Martina; Wilson, David S.; Simeoni, Eleonora; Hubbell, Jeffrey A.

In: Scientific Reports, Vol. 5, 17622, 03.12.2015.

Research output: Contribution to journalArticle

Damo, Martina ; Wilson, David S. ; Simeoni, Eleonora ; Hubbell, Jeffrey A. / TLR-3 stimulation improves anti-tumor immunity elicited by dendritic cell exosome-based vaccines in a murine model of melanoma. In: Scientific Reports. 2015 ; Vol. 5.
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