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Journal of Translational Medicine
Published in: Journal of Translational Medicine 1/2007

Open Access 01-12-2007 | Research

An epigenetic vaccine model active in the prevention and treatment of melanoma

Authors: A Nazmul H Khan, William J Magner, Thomas B Tomasi

Published in: Journal of Translational Medicine | Issue 1/2007

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Abstract

Background

Numerous immune genes are epigenetically silenced in tumor cells and agents such as histone deacetylase inhibitors (HDACi), which reverse these effects, could potentially be used to develop therapeutic vaccines. The conversion of cancer cells to antigen presenting cells (APCs) by HDACi treatment could potentially provide an additional pathway, together with cross-presentation of tumor antigens by host APCs, to establish tumor immunity.

Methods

HDACi-treated B16 melanoma cells were used in a murine vaccine model, lymphocyte subset depletion, ELISpot and Cytotoxicity assays were employed to evaluate immunity. Antigen presentation assays, vaccination with isolated apoptotic preparations and tumorigenesis in MHC-deficient mice and radiation chimeras were performed to elucidate the mechanisms of vaccine-induced immunity.

Results

HDACi treatment enhanced the expression of MHC class II, CD40 and B7-1/2 on B16 cells and vaccination with HDACi-treated melanoma cells elicited tumor specific immunity in both prevention and treatment models. Cytotoxic and IFN-γ-producing cells were identified in splenocytes and CD4+, CD8+ T cells and NK cells were all involved in the induction of immunity. Apoptotic cells derived from HDACi treatments, but not H2O2, significantly enhanced the effectiveness of the vaccine. HDACi-treated B16 cells become APCs in vitro and studies in chimeras defective in cross presentation demonstrate direct presentation in vivo and short-term but not memory responses and long-term immunity.

Conclusion

The efficacy of this vaccine derives mainly from cross-presentation which is enhanced by HDACi-induced apoptosis. Additionally, epigenetic activation of immune genes may contribute to direct antigen presentation by tumor cells. Epigenetically altered cancer cells should be further explored as a vaccine strategy.
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Metadata
Title
An epigenetic vaccine model active in the prevention and treatment of melanoma
Authors
A Nazmul H Khan
William J Magner
Thomas B Tomasi
Publication date
01-12-2007
Publisher
BioMed Central
Published in
Journal of Translational Medicine / Issue 1/2007
Electronic ISSN: 1479-5876
DOI
https://doi.org/10.1186/1479-5876-5-64

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