RRC ID 75780
著者 Wakimoto H, Abe J, Tsunoda R, Aoyagi M, Hirakawa K, Hamada H.
タイトル Intensified antitumor immunity by a cancer vaccine that produces granulocyte-macrophage colony-stimulating factor plus interleukin 4.
ジャーナル Cancer Res
Abstract Vaccination with irradiated tumor cells genetically modified to secrete granulocyte-macrophage colony-stimulating factor (GM-CSF tumor vaccine) induces a potent systemic antitumor immunity. To develop a protocol for cancer therapy to further augment the host immune response, we examined the effects of the GM-CSF tumor vaccines simultaneously producing additional cytokines. We prepared cancer vaccines expressing double cytokines by sequential recombinant retrovirus-mediated genetic transductions. We then used a murine intracerebral tumor model in which the GM-CSF tumor vaccine was less effective in immunopotentiation and evaluated tumor vaccines producing various cytokines in conjunction with GM-CSF. The cytokine combination of GM-CSF and interleukin 4 induced more potent antitumor immunity than GM-CSF alone. An in vivo depletion test showed that CD4+, CD8+, and asialoGM1+ cells were required for the optimum function of the GM-CSF plus interleukin 4 tumor vaccine. Histological examinations revealed infiltration of inflammatory cells at the site of tumor cell challenge as well as at the site of vaccination, indicating the induction of a systemic antitumor immune response which reached the central nervous system. Our findings suggest the feasibility of applying the intensified vaccination strategy to treat human cancers including malignant brain tumors.
巻・号 56(8)
ページ 1828-33
公開日 1996-4-15
PMID 8620500
MeSH 3T3 Cells Animals Brain Neoplasms / immunology Brain Neoplasms / pathology Brain Neoplasms / secondary Brain Neoplasms / therapy* Cytokines / biosynthesis Female Genetic Vectors Granulocyte-Macrophage Colony-Stimulating Factor / biosynthesis* Humans Immunotherapy* Interleukin-4 / biosynthesis* Melanoma, Experimental / immunology Melanoma, Experimental / pathology Melanoma, Experimental / secondary* Melanoma, Experimental / therapy Mice Mice, Inbred C57BL Polymerase Chain Reaction Retroviridae Vaccines, Synthetic*
IF 9.727
リソース情報
遺伝子材料 pMFGmGM-CSF (RDB01438) pMFGmIL2 (RDB01441) pMFGmIL3 (RDB01442) pMFGmIL4 (RDB01443) pMFGmIL6 (RDB01444) pMFGmIL7 (RDB01445) pMFGmTNF alpha (RDB01449) pMFGmLT (RDB01451) pMFGmG-CSF (RDB01452) pMFGmLIF (RDB01456)