Antitumor immunity induced by tumor cells engineered to express a membrane-bound form of IL-2.
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.
Chang
Mi-Ra
MR
Department of Biochemistry, College of Natural Sciences, Chungnam National University, Daejeon 305-764, Republic of Korea.
Lee
Woong-Hee
WH
Choi
Jin-Wha
JW
Park
Sun-Ok
SO
Paik
Sang-Gi
SG
Kim
Young Sang
YS
D000818:Animals; D015496:CD4-Positive T-Lymphocytes; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology*; D005260:Female; D005818:Genetic Engineering; D007376:Interleukin-2 / Q000235:genetics* / Q000378:metabolism; D008175:Lung Neoplasms / Q000276:immunology* / Q000556:secondary / Q000628:therapy; D008213:Lymphocyte Activation; D008546:Melanoma, Experimental / Q000235:genetics / Q000276:immunology* / Q000517:prevention & control*; D051379:Mice; D008810:Mice, Inbred C57BL; D013154:Spleen / Q000276:immunology; D015996:Survival Rate; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014611:Vaccination
D019496:Cancer Vaccines; D007376:Interleukin-2