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- Title
Vaccine effect of granulocyte–macrophage colony-stimulating factor or CD80 gene-transduced murine hematopoietic tumor cells and their cooperative enhancement of antitumor immunity.
- Authors
Nakazaki, Y; Tani, K; Lin, Z-T; Sumimoto, H; Hibino, H; Tanabe, T; Wu, M-S; Izawa, K; Hase, H; Takahashi, S; Tojo, A; Azuma, M; Hamada, H; Mori, S; Asano, S
- Abstract
To develop immunogene therapy targeting minimal residual hematopoietic tumor cells in patients, we transduced murine GM-CSF or CD80 gene into murine WEHI 3B myelomonocytic leukemia and EL-4 thymic lymphoma cells using retroviral vectors and evaluated their effects on inducing antitumor responses in syngeneic host mice. Subcutaneously injected GM-CSF- and CD80 gene-transduced WEHI 3B (GMCSF/WEHI/3.2 or CD80/WEHI/1.8, respectively) cells lost their original tumorigenicity in immunocompetent syngeneic mice. Results from tumor inoculation experiments using athymic nude mice suggested that the rejection of GMCSF/WEHI/3.2 in immunocompet- ent mice depended fully on T cells and that of CD80/WEHI/1.8 depended partly on T cells and partly on NK cells. In both WEHI 3B and EL-4 models, irradiated GM-CSF gene-transduced cells provided strong immunoprotection against wild-type cells, but irradiated CD80 gene- transduced cells did not. A remarkably high cooperative effect was obtained when irradiated GMCSF/EL-4 and CD80/EL-4 were inoculated together. These results suggested that the tumor vaccine effect is efficiently enhanced by GM-CSF gene transduction and CD80 gene transduction induces some protective antitumor immunity in co operation with GM-CSF gene transduction.
- Subjects
GRANULOCYTE-macrophage colony-stimulating factor; GENE therapy; CANCER vaccines
- Publication
Gene Therapy, 1998, Vol 5, Issue 10, p1355
- ISSN
0969-7128
- Publication type
Article
- DOI
10.1038/sj.gt.3300726