|Title / Titel||Development and implementation of anti-tumor vaccination methods|
|Abstract (PDF, 14 KB)|
|Summary / Zusammenfassung||Our goal is to implement optimized anti-cancer immunotherapies. To this end we will combine a powerful new vaccination method that is the Gene-Gun delivery with standard treatments such as chemotherapies.
The Gene-Gun delivery allows a painless, efficient and reproducible delivery of nucleic acids in the skin. This results in the development of an immune response targeted against the protein encoded by the foreign nucleic acid. Using nucleic acids coding for proteins expressed in the tumor only such as NY-ESO-1, the Gene-Gun method can help in boosting the immune recognition of tumors. In order to further enhance the efficacy of the Gene-Gun, we are seeking to optimise the nucleic acid sequence and NY-ESO-1's immunogenicity. The new recombinant versions of NY-ESO-1 genes are tested in vitro and in vivo (in mice) in comparaison to the wild type gene in order to identify and validate the advantageous new features.
In addition, we study the compatibility and eventual synergies between anti-tumor vaccination and chemotherapy. To this end, we first analyse the performances of the immune system of cancer patients undergoing standard treatments. Of main focus, we study the immunosuppressive mechanisms that naturally limit the development of an anti-tumor immunity. Some of these "immune tolerance" mechanisms are decreased as a side effect of certain chemotherapy regimen. We are studying the potency of chemotherapeutic drug to induce this side effect and defining the time point at which immunosuppressive mechanisms are most reduced during a chemotherapeutic treatment. This time point would correspond to an immune status most favorable for anti-tumor vaccination.
From these pre-clinical studies, we will design clinical trials combining standard chemotherapy and improved immunotherapy for the treatment of advanced cancer patients.
|Publications / Publikationen||Therapeutic anti-tumor immunity triggered by injections of immunostimulating single-stranded RNA.
Scheel B, Aulwurm S, Probst J, Hoerr I, Rammensee HG, Weller M, Pascolo S.
Eur J Immunol. 2006 Oct 2; 36(10):2807-2816Rammensee HG, Pascolo S. Production and characterization of amplified tumor-derived cRNA libraries to be used as vaccines against metastatic melanomas.
Carralot JP, Weide B, Schoor O, Probst J, Scheel B, Teufel R, Hoerr I, Garbe C,
Genet Vaccines Ther. 2005 Aug 22;3:6.Polarization of immunity induced by direct injection of naked sequence-stabilized mRNA vaccines.
Carralot JP, Probst J, Hoerr I, Scheel B, Teufel R, Jung G, Rammensee HG, Pascolo S.
Cell Mol Life Sci. 2004 Sep;61(18):2418-24.
|Keywords / Suchbegriffe||Vaccine, immunotherapy, cancer, nucleic acids, chemotherapy|
|Project leadership and contacts /
Projektleitung und Kontakte
|Funding source(s) /
|Forschungskredit der Universität Zürich
Core-grant, LICR, CRI, SFO (Stiftung für die Forschung in der Onkologie, Zürich)
|In collaboration with /
In Zusammenarbeit mit
|Duration of Project / Projektdauer||Jun 2006 to Jun 2009|