Neuroblastome-Immunolog.Target Validierg


In this NGFN-plus grant, the results from gene expression profiling, which were established in the previous NGFN grant period, will be used to expand established and to delineate novel immunotherapeutic strategies for pediatric tumors using neuroblastoma as a model. First, we will analyze the expression of all immunologically relevant genes known up date and correlate findings with prognostic factors (stage of the disease; MYCN amplification), with the goal to establish an immunological signature of neuroblastoma. With this signature, we will select potential antigens and factors involved in antigen processing and presentation for further analysis of genes relevant to the expansion of established and the delineation of novel immunotherapeutic strategies. Second, we will generate and characterize expression plasmids encoding for target genes, which can be used for genetic vaccination. Selected genes will be potential antigens and factors to optimize antigen processing and presentation (i.e. cytokines, chemokines, chaperones). The integrity and the function of such expression plasmids will be tested in vitro and in vivo. Third, effects and mechanisms of genetic immunization will be analyzed in two syngeneic and spontaneous mouse models highly relevant to human neuroblastoma including the NXS2- and the MYCN transgenic-model. In these models, optimal prime/boost schedules will be determined using two different modes of clinically approved DNA delivery systems, including in vivo D
Head of Project:

Prof. Dr. Holger Lode
Charité - Universitätsmedizin Berlin
Department of Pediatrics Endocrinology, Gastroenterology and Metabolic medicine CVK
Tel. 450-559217
Fax 450-559917
holger.lode@charite.de
Additional Head of Project:

Dr. Nicole Huebener
Additional Member of Project:

Dipl.biol. Alexander Stermann
Begin/End of Project:

06/2008 - 05/2011
Funded by:

Bundesministerium für Bildung und Forschung
Publications:

Huebener N, Fest S, Strandsby A, Michalsky E, Preissner R, Zeng Y, Gaedicke G, Lode HN. A rationally designed tyrosine hydroxylase DNA vaccine induces specific antineuroblastoma immunity. Mol Cancer Ther. 2008 Jul;7(7):2241-51.