Unknown

Dataset Information

0

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


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.

SUBMITTER: Damo M 

PROVIDER: S-EPMC4668567 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature

altmetric image

Publications

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

Damo Martina M   Wilson David S DS   Simeoni Eleonora E   Hubbell Jeffrey A JA  

Scientific reports 20151203


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.  ...[more]

Similar Datasets

| S-EPMC4111144 | biostudies-literature
| S-EPMC4556596 | biostudies-literature
| S-EPMC3437589 | biostudies-literature
| S-EPMC5609833 | biostudies-literature
| S-EPMC4399865 | biostudies-literature
| S-EPMC4912940 | biostudies-other
| S-EPMC8609477 | biostudies-literature
| S-EPMC2755640 | biostudies-literature
| S-EPMC4002214 | biostudies-literature
| S-EPMC2518883 | biostudies-literature