CURE OF ESTABLISHED, INTRACEREBRAL RAT GLIOMAS INDUCED BY THERAPEUTICIMMUNIZATIONS WITH TUMOR-CELLS AND PURIFIED APC OR ADJUVANT IFN-GAMMATREATMENT

We have previously reported that immunizations with mutagen-induced im munogenic variants of a weakly immunogenic rat glioma could protect ag ainst isografts of the original turner cells. In this study we show th at prolonged survival and cures of rats with established gliomas in th eir brains can be achieved by therapeutic immunizations with turner ce ll mutants, combined with in vitro and in vivo interferon (IFN)-gamma (adjuvant) treatment, or tumor cells admixed with semipurified syngene ic dendritic cells. Cure of rats with established intracerebral glioma s was possible when immunizations were initialed up to 5 days after in tracerebral isografting of original tumor cells. Unexpectedly, immuniz ations combined with in vitro and in vivo IFN-gamma treatment or with admired semipurified dendritic cells equalized the immunogenic potenti al of the original tumor cells and thtr. of mutagen-induced immunogeni c cell variants (tum(-)). This demonstrates that effective immunizatio ns against a weakly immunogenic brain tumor can be achieved by differe nt adjuvant concepts. The therapeutic effect oi immunizations with tum or cells admixed with semipurified dendritic cells was highly signific ant in female rats, whereas only occasional cures and prolonged surviv al were recorded in male rats. The overall results show that therapeut ic immunizations can indeed be effective against an established and gr owing intracerebral tumor.