Antitumor immunity induced by tumor cells engineered to express a membrane-bound form of IL-2.
- Author:
Mi Ra CHANG
1
;
Woong Hee LEE
;
Jin Wha CHOI
;
Sun Ok PARK
;
Sang Gi PAIK
;
Young Sang KIM
Author Information
1. Department of Biochemistry, College of Natural Sciences, Chungnam National University, Daejeon 305-764, Republic of Korea. young@cnu.ac.kr
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
cancer vaccines;
immunotherapy, active;
interleukin-2;
neoplasm metastasis;
T lymphocytes, cytotoxic
- MeSH:
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
- From:Experimental & Molecular Medicine
2005;37(3):240-249
- CountryRepublic of Korea
- Language:English
-
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.
