Research article

Use of a recombinant Salmonella enterica serovar Typhimurium strain expressing C-Raf for protection against C-Raf induced lung adenoma in mice

Ivaylo Gentschev^1* , Joachim Fensterle^1* , Andreas Schmidt^1* , Tamara Potapenko¹ , Jakob Troppmair² , Werner Goebel³ and Ulf R Rapp¹

¹  Institut für Medizinische Strahlenkunde und Zellforschung (MSZ), University of Wuerzburg, D-97078 Wuerzburg, Germany

²  Daniel-Swarovski-Research Laboratory, Department of General and Transplant Surgery, Innsbruck Medical University, Innsbruck, Austria

³  Department of Microbiology, University of Wuerzburg, D-97074 Wuerzburg, Germany

author email corresponding author email* Contributed equally

BMC Cancer 2005, 5:15doi:10.1186/1471-2407-5-15

Published:	9 February 2005

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 α-hemolysin and expressed in secreted form by an attenuated aroA Salmonella enterica serovar Typhimurium strain via the α-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.