Antitumor immunity induced by tumor cells engineered to express a membrane-bound form of IL-2
Experimental & Molecular Medicine
;
: 240-249, 2005.
Article
in English
| WPRIM
| ID: wpr-201937
ABSTRACT
Transduction of cytokine gene into tumor cells is a promising method of tumor therapy, but the value is limited by accompanying side effects. To focus antitumor immune response to tumor antigen-specific CTL, we developed an antitumor vaccine by transfecting modified IL-2 gene in a membrane-bound form (mbIL-2) into B16F10 melanoma cells. The mbIL-2 clone showed reduced tumorigenicity and metastatic ability, and inhibited metastasis and prolonged the survival of mice against B16F10 cells. The inhibition of B16F10 metastasis by mbIL-2 was accompanied by the increment of CD8+ T cells. The metastasis of mbIL-2 clone was significantly increased in the CD8+ T cell-depleted mice, but not in CD4+ T cell depleted mice. Spleen cells immunized with the mbIL-2 clone showed higher CTL activity towards B16F10 cells than those immunized with control cells. The size of CD8+ T cell population in the lung of mice injected with the mbIL-2 clone was markedly greater than that of mice injected with B16F10 cells, but there was no detectible change in CD4+ and CD8+ T cell populations of lymph nodes and spleen. These results suggest that when the mbIL-2 clone is introduced into the blood stream, it migrates mainly to lung and activates CD8+ T cells in situ, possibly by direct priming. Such a tumor vaccine may ameliorate the toxic side effects encountered with conventional cytokine gene therapy.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Spleen
/
Melanoma, Experimental
/
Lymphocyte Activation
/
T-Lymphocytes, Cytotoxic
/
CD4-Positive T-Lymphocytes
/
Genetic Engineering
/
Survival Rate
/
Interleukin-2
/
Vaccination
/
CD8-Positive T-Lymphocytes
Limits:
Animals
Language:
English
Journal:
Experimental & Molecular Medicine
Year:
2005
Type:
Article
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