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Am J Reprod Immunol. 2011 Jun;65(6):597-609. doi: 10.1111/j.1600-0897.2010.00968.x. Epub 2011 Jan 18.

Enhanced stimulation of anti-ovarian cancer CD8(+) T cells by dendritic cells loaded with nanoparticle encapsulated tumor antigen.

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  • 1Department of Dermatology, Yale University, New Haven, CT 06520, USA.

Abstract

PROBLEM:

Dendritic cell (DC)-based cancer therapies are favored approaches to stimulate anti-tumor T-cell responses. Unfortunately, tolerance to tumor antigens is difficult to overcome. Biodegradable poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NP) are effective reagents in the delivery of drugs and tumor-associated antigens (TAA). In this study, we assessed the capacity of a PLGA NP-based delivery system to augment CD8 T-cell responses to ovarian cancer TAA.

METHOD OF STUDY:

Human DC were generated from blood monocytes by conventional in vitro differentiation and loaded with either soluble tumor lysate or NP/lysate conjugates (NPL). These antigen-loaded DC were then used to stimulate autologous CD8(+) T cells. Cytokine production and activation markers were evaluated in the CD8(+) T cells.

RESULTS:

DC loading with NPL increased cytokine production by stimulated CD8 T cells and induced T-cell expression of cell surface co-stimulatory molecules, typical of anti-tumor immune responses. In contrast, delivery of naked tumor lysate antigens preferentially induced a T-cell profile characteristic of tolerization/exhaustion.

CONCLUSION:

These findings indicate that delivery of TAA in NP enables DC to efficiently activate anti-tumor CD8(+) T cells. PLGA NP encapsulation of tumor-derived lysate protein antigens is an encouraging new preparative methodology for DC-based vaccination meriting clinical testing.

© 2011 John Wiley & Sons A/S.

PMID:
21241402
[PubMed - indexed for MEDLINE]
PMCID:
PMC3082607
Free PMC Article
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