| RRC ID |
75780
|
| Author |
Wakimoto H, Abe J, Tsunoda R, Aoyagi M, Hirakawa K, Hamada H.
|
| Title |
Intensified antitumor immunity by a cancer vaccine that produces granulocyte-macrophage colony-stimulating factor plus interleukin 4.
|
| Journal |
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.
|
| Volume |
56(8)
|
| Pages |
1828-33
|
| Published |
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
|
| Resource |
| DNA material |
pMFGmGM-CSF (RDB01438)
pMFGmIL2 (RDB01441)
pMFGmIL3 (RDB01442)
pMFGmIL4 (RDB01443)
pMFGmIL6 (RDB01444)
pMFGmIL7 (RDB01445)
pMFGmTNF alpha (RDB01449)
pMFGmLT (RDB01451)
pMFGmG-CSF (RDB01452)
pMFGmLIF (RDB01456) |
