Intensified Antitumor Immunity by a Cancer Vaccine That Produces Granulocyte-Macrophage Colony-stimulating Factor plus Interleukin 4

摘要: Vaccination with irradiated tumor cells genetically modified to secrete granulocyte-macrophage colony-stimulating factor (GM-CSF vaccine) induces a potent systemic antitumor immunity. To develop protocol for cancer therapy further augment the host immune response, we examined effects of GM-CSF vaccines simultaneously producing additional cytokines. We prepared expressing double cytokines by sequential recombinant retrovirus-mediated genetic transductions. then used murine intracerebral model in which vaccine was less effective immunopotentiation and evaluated various conjunction GM-CSF. The cytokine combination interleukin 4 induced more immunity than alone. An vivo depletion test showed that CD4+, CD8+, asialoGM1+ were required optimum function plus vaccine. Histological examinations revealed infiltration inflammatory at site cell challenge as well vaccination, indicating induction response reached central nervous system. Our findings suggest feasibility applying intensified vaccination strategy treat human cancers including malignant brain tumors.