Entwicklung und klinische Anwendung neuer retroviraler Vektorsysteme fuer somatische Gentherapie. Retrovirale Vektorsysteme fuer somatische Gentherapie Schlussbericht

The aim of the given project was to introduce clinical gene therapeutic studies relying on the use of retroviral vectors in Hamburg. During the period of support we were able to establish the technological basis for the successful execution of the supposed clinical trials. Moreover, the infrastructure to conduct gene transfer in accordance with the rules of 'good manufacturing practice' was created by the foundation of two small German biotech companies. In cooperation with our partner Heinrich-Pette-Institute (HPI) we initiated two clinical studies, which are going to start in 1999 and at the beginning of 2000, respectively. Because of the large interest of other clinics, the clinical study on adoptive immunotherapy with gene-modified T lymphocytes designed during this project will be carried out as an international phase I/II study under the direction of the Hamburg BMT center. During the project, efficient infection protocols for hematopoietic stem and progenitor cells and for the enrichment of gene-modified cells were developed. It was shown for the first time that the matrix protein fibronectin facilitates retroviral gene transfer into T lymphocytes. Recently, the first protocol for clinical gene transfer in the absence of bovine serum has been published by our group. Thereby, an important problem of biological safety during ex vivo transduction has been solved. In cooperation with or partner HPI, new retroviral vectors have been developed, which are characterized by better expression features in hematopoietic cells. (orig.)Available from TIB Hannover: DtF QN1(76,23) / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEDEGerman