Use of a Recombinant Salmonella Enterica Serovar Typhimurium Strain Expressing C-Raf for Protection Against C-Raf Induced Lung Adenoma in Mice

Overview

Journal BMC Cancer

Publisher Biomed Central

Specialty Oncology

Date 2005 Feb 11

PMID 15703070

Citations 14

Authors

Ivaylo Gentschev

Joachim Fensterle

Andreas Schmidt

Tamara Potapenko

Jakob Troppmair

Werner Goebel

Ulf R Rapp

Affiliations

Soon will be listed here.

Abstract

Background: Serine-threonine kinases of the Raf family (A-Raf, B-Raf, C-Raf) are central players in cellular signal transduction, and thus often causally involved in the development of cancer when mutated or over-expressed. Therefore these proteins are potential targets for immunotherapy and a possible basis for vaccine development against tumors. In this study we analyzed the functionality of a new live C-Raf vaccine based on an attenuated Salmonella enterica serovar Typhimurium aroA strain in two Raf dependent lung tumor mouse models.

Methods: The antigen C-Raf has been fused to the C-terminal secretion signal of Escherichia coli alpha-hemolysin and expressed in secreted form by an attenuated aroA Salmonella enterica serovar Typhimurium strain via the alpha-hemolysin secretion pathway. The effect of the immunization with this recombinant C-Raf strain on wild-type C57BL/6 or lung tumor bearing transgenic BxB mice was analyzed using western blot and FACS analysis as well as specific tumor growth assays.

Results: C-Raf antigen was successfully expressed in secreted form by an attenuated Salmonella enterica serovar Typhimurium aroA strain using the E. coli hemolysin secretion system. Immunization of wild-type C57BL/6 or tumor bearing mice provoked specific C-Raf antibody and T-cell responses. Most importantly, the vaccine strain significantly reduced tumor growth in two transgenic mouse models of Raf oncogene-induced lung adenomas.

Conclusions: The combination of the C-Raf antigen, hemolysin secretion system and Salmonella enterica serovar Typhimurium could form the basis for a new generation of live bacterial vaccines for the treatment of Raf dependent human malignancies.

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