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Open Access 01-12-2011 | Research

Combination immunotherapy and active-specific tumor cell vaccination augments anti-cancer immunity in a mouse model of gastric cancer

Authors: Natasja K van den Engel, Dominik Rüttinger, Margareta Rusan, Robert Kammerer, Wolfgang Zimmermann, Rudolf A Hatz, Hauke Winter

Published in: Journal of Translational Medicine | Issue 1/2011

Abstract

Background

Active-specific immunotherapy used as an adjuvant therapeutic strategy is rather unexplored for cancers with poorly characterized tumor antigens like gastric cancer. The aim of this study was to augment a therapeutic immune response to a low immunogenic tumor cell line derived from a spontaneous gastric tumor of a CEA424-SV40 large T antigen (CEA424-SV40 TAg) transgenic mouse.

Methods

Mice were treated with a lymphodepleting dose of cyclophosphamide prior to reconstitution with syngeneic spleen cells and vaccination with a whole tumor cell vaccine combined with GM-CSF (a treatment strategy abbreviated as LRAST). Anti-tumor activity to subcutaneous tumor challenge was examined in a prophylactic as well as a therapeutic setting and compared to corresponding controls.

Results

LRAST enhances tumor-specific T cell responses and efficiently inhibits growth of subsequent transplanted tumor cells. In addition, LRAST tended to slow down growth of established tumors. The improved anti-tumor immune response was accompanied by a transient decrease in the frequency and absolute number of CD4⁺CD25⁺FoxP3⁺ T cells (Tregs).

Conclusions

Our data support the concept that whole tumor cell vaccination in a lymphodepleted and reconstituted host in combination with GM-CSF induces therapeutic tumor-specific T cells. However, the long-term efficacy of the treatment may be dampened by the recurrence of Tregs. Strategies to counteract suppressive immune mechanisms are required to further evaluate this therapeutic vaccination protocol.

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Title: Combination immunotherapy and active-specific tumor cell vaccination augments anti-cancer immunity in a mouse model of gastric cancer
Authors: Natasja K van den Engel
Dominik Rüttinger
Margareta Rusan
Robert Kammerer
Wolfgang Zimmermann
Rudolf A Hatz
Hauke Winter
Publication date: 01-12-2011
Publisher: BioMed Central
Published in: Journal of Translational Medicine / Issue 1/2011
Electronic ISSN: 1479-5876
DOI: https://doi.org/10.1186/1479-5876-9-140

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Conclusions

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