Gentechnische Modifizierung von Tumorzellen zur Entwicklung einer Gentherapie des Prostata- und Mammakarzinoms Schlussbericht

This project was designed to develop autologous, genetically-engineered tumor cell vaccines, based on the use of micrometastatic tumor cell isolates from bone marrow biopsies, for patients with prostate and breast cancer. Because of natural limitations in starting cell numbers and their inherent low proliferative capacity the micrometastatic tumor cells were to be immortalized through microinjection of SV40-large T antigen DNA. A dual vector system, based on Cre/LoxP-mediated site-specific deletion created by Prof. T. Blankenstein and coworkers (Human Gene Therapy 8: 1695-1700, 1997) was to be used for safety purposes, enabling the large T Ag encoding DNA to be excised from the tumor cells at a later stage. Stable, proliferating lines were to be phenotypically and molecularly characterized to certify their tumor origin and analyzed for their immunogenicity using in vitro experiments with effector cells derived from patients. Further genetic modification of the tumor cells through introduction of cDNAs encoding various cytokine genes and the B7.1 costimulatory molecule were to be analyzed for their capacity to improve tumor cell antigenicity. In vivo studies were to be made using a huSCID mouse model. Studies analyzing immune responses in cancer patients were to be made to understand the status of host-tumor interactions. (orig.)Available from TIB Hannover: DtF QN1(76,10) / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEBundesministerium fuer Bildung und Forschung (BMBF), Bonn (Germany)DEGerman