use of weakened version of diarrhea-causing bacteria effective against her2+ breast

[Lani]

cancer in experimental model--there was a 74% reduction in tumors only 7 days after a mouse with her2+ bc was infected with the weakened Shigella bacteria

Shigella Mediated Depletion of Macrophages in a Murine Breast Cancer Model Is Associated with Tumor Regression

Katharina Galmbacher1#¤a, Martin Heisig1,2#, Christian Hotz1¤b, Joerg Wischhusen3, Antoine Galmiche1¤c, Birgit Bergmann1,2, Ivaylo Gentschev1¤d, Werner Goebel2¤e, Ulf R. Rapp1¤f, Joachim Fensterle1¤g*
1 Institut für Medizinische Strahlenkunde und Zellforschung, Universität Würzburg, Würzburg, Germany, 2 Institut für Mikrobiologie, Biozentrum, Universität Würzburg, Würzburg, Germany, 3 Universitätsfrauenklinik Würzburg, Würzburg, Germany
Abstract

A tumor promoting role of macrophages has been described for a transgenic murine breast cancer model. In this model tumor-associated macrophages (TAMs) represent a major component of the leukocytic infiltrate and are associated with tumor progression. Shigella flexneri is a bacterial pathogen known to specificly induce apotosis in macrophages. To evaluate whether Shigella-induced removal of macrophages may be sufficient for achieving tumor regression we have developed an attenuated strain of S. flexneri (M90TΔaroA) and infected tumor bearing mice. Two mouse models were employed, xenotransplantation of a murine breast cancer cell line and spontanous breast cancer development in MMTV-HER2 transgenic mice. Quantitative analysis of bacterial tumor targeting demonstrated that attenuated, invasive Shigella flexneri primarily infected TAMs after systemic administration. A single i.v. injection of invasive M90TΔaroA resulted in caspase-1 dependent apoptosis of TAMs followed by a 74% reduction in tumors of transgenic MMTV-HER-2 mice 7 days post infection. TAM depletion was sustained and associated with complete tumor regression.

These data support TAMs as useful targets for antitumor therapy and highlight attenuated bacterial pathogens as potential tools.

http://www.plosone.org/article/info%...l.pone.0009572