Anti-metastatic vaccination of tumor-bearing mice with IL-2-gene-inserted tumor cells.
IL-2 gene was introduced through retroviral vectors into the highly malignant and poorly immunogenic 3LL-D122 clone. Both high and low D122-IL-2 secretors showed elimination of tumorigenicity in syngeneic immune-competent mice; however, in nude mice only the high IL-2 secretor showed reduced tumorigenicity as compared with parental D122 cells. Also, following intravenous inoculation, only the high IL-2 secretor showed reduced generation of metastases, whereas the low IL-2 secretors were as highly metastatic as parental cells. These results seem to indicate that low levels of IL-2 secreted by tumor cells are sufficient to activate T cells, while higher levels are needed in order to activate non-T-cell effectors. D122-IL-2 secretors induced high levels of anti-tumor CTL, while their sensitivity to the lytic activity of these CTL was similar to the sensitivity of D122 cells, thus indicating that the elevation of immunogenicity of IL-2 secretors was essentially due to the secreted IL-2. In accordance with CTL induction, pre-immunization with IL-2 secretors protected mice against subsequent challenge of parental cells. Moreover, immunization in an "immunotherapy protocol" i.e., vaccination of mice carrying an established tumor of parental D122 cells with inactivated D122-IL2 infectants, almost completely eliminated the generation of lung metastases by D122 cells, thus providing a rationale for the use of IL-2 gene transferred tumor cells as a modality for treatment of metastasis.
Porgador
A
A
Department of Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
Gansbacher
B
B
Bannerji
R
R
Tzehoval
E
E
Gilboa
E
E
Feldman
M
M
Eisenbach
L
L
D000818:Animals; D002277:Carcinoma / Q000276:immunology / Q000628:therapy*; D003602:Cytotoxicity, Immunologic; D007167:Immunotherapy; D007376:Interleukin-2 / Q000502:physiology*; D008175:Lung Neoplasms / Q000276:immunology / Q000628:therapy*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014162:Transfection; D014611:Vaccination
D007376:Interleukin-2