Exp Mol Med.  2005 Jun;37(3):240-249.

Antitumor immunity induced by tumor cells engineered to express a membrane-bound form of IL-2

• Chang MR
• Lee WH
• Choi JW
• Park SO
• Paik SG
• Kim YS

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.

Keyword

cancer vaccines; immunotherapy, active; interleukin-2; neoplasm metastasis; T lymphocytes, cytotoxic

MeSH Terms

Animals
CD4-Positive T-Lymphocytes
CD8-Positive T-Lymphocytes/immunology
Cancer Vaccines/*immunology
Female
*Genetic Engineering
Interleukin-2/*genetics/metabolism
Lung Neoplasms/*immunology/secondary/therapy
Lymphocyte Activation
Melanoma, Experimental/genetics/*immunology/*prevention & control
Mice
Mice, Inbred C57BL
Research Support, Non-U.S. Gov't
Spleen/immunology
Survival Rate
T-Lymphocytes, Cytotoxic/immunology
Vaccination