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Induction of anti-tumor cytotoxic T cell responses through PLGA-nanoparticle mediated antigen delivery

Paper ID Volume ID Publish Year Pages File Format Full-Text
7223 541 2011 13 PDF Available
Title
Induction of anti-tumor cytotoxic T cell responses through PLGA-nanoparticle mediated antigen delivery
Abstract

Nanotechnology-based antigen delivery has been developing as a vaccine strategy due to its dose-sparing and prolonged antigen presentation features. In the current study, we examined the feasibility of nanoparticle (NP)-mediated delivery of antigenic peptides to efficiently induce cytotoxic T lymphocyte responses against tumor-associated self-antigens in C57BL/6 mouse models. The biodegradable poly(d,l-lactide-co-glycolide) nanoparticle (PLGA-NP) carrying murine melanoma antigenic peptides, hgp10025–33 and TRP2180–188, were prepared by double emulsion method. Efficient uptake of PLGA-NP by murine dendritic cells was shown in vitro and in vivo, using NP labeled with the fluorescent dye DiD. Intradermal injection of peptide-loaded PLGA-NP into mice induced antigen-specific T cell responses more strongly than the peptides mixed with Freund’s adjuvant. More importantly, vaccination with PLGA-NP carrying both TRP2180–188 and a toll-like receptor 4 agonist, monophosphoryl lipid A, significantly delayed growth of subcutaneously inoculated B16 melanoma cells in a prophylactic setting. Furthermore, the anti-tumor activity of NP-mediated peptide vaccination was significantly augmented by combined treatment with interferon-γ, which might prevent tumor escape through up-regulation of MHC class I expression on tumor cells. Our findings demonstrate the feasibility of NP-mediated antigen delivery for cancer immunotherapy, in particular when immune escape mechanisms of tumor cells are blocked simultaneously.

Keywords
Nanoparticle; Peptide; Toll-like receptor 4 agonist; Tumor immunity; Interferon-γ; Immune escape
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Induction of anti-tumor cytotoxic T cell responses through PLGA-nanoparticle mediated antigen delivery
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 32, Issue 14, May 2011, Pages 3666–3678
Authors
, , , , , , , , , ,
Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us