Bacteria as immunotherapeutics against tumors

Joachim Fensterle^1,5, Jochen Stritzker², Yvonne Dombrowski¹, Andreas Schmidt¹, Miso Kursar³, Ivo Gentschev¹, Werner Goebel³, Eva B. Bröcker⁴, Jürgen C. Becker⁴ and Ulf R. Rapp¹

¹ Inst. f. Med. Strahlenkunde und Zellforschung (MSZ), University of Würzburg, Germany

² Inst. for Microbiology, University of Würzburg, Germany

³ Max-Planck Institute for Infection Biology, Berlin, Germany

⁴ Department of Dermatology, University of Würzburg, Germany

⁵ theraimmune GmbH, Würzburg, Germany

Various mechanisms in cancerous diseases impede an efficient attack by the immune system. One example is the suppressive role of CD4⁺ CD25⁺ T-cells which are especially efficient in inhibiting memory CD8⁺ T-cell responses being the most important branch of the immune system to combat cancer. We have shown that immune induction by bacteria is much less sensitive against inhibition by this cell type and we have developed a tumor vaccine based on C-Raf producing recombinant Salmonella expressing the Escherichia coli type I hemolysin secretion machinery. As we were able to detect B-Raf specific antibodies in 8.5 % of 381 analyzed sera of melanoma patients, a Raf based immunization approach using recombinant attenuated intracellular bacteria as carriers might be a favourable approach for future tumor vaccines.