Induction of immune response by IL-6 gene-modified leukemia cells

Abstract

Human IL-6 gene was transduced into FBL-3 murine erythroleukemia cellsin vitro by calcium phosphate co-participation. After selection in the presence of G418, limiting dilution and biological activity assay, G418 resistant clone that secreted the highest level of IL-6 (225.6 U/ml) was selected out of 24 IL-6-secreting clones. The FBL-3 cells secreting the highest level of IL-6 (FBL-3-IL-6) showed decreased growth potential and clonogenicityin vitro. Inhibition of cell growth and clone formation was found to be closely related to the level of IL-6 secretion. FBL-3-IL-6 cells grew more slowly than wild-type FBL-3 leukemia cells and FBL-3 cells secreting lower level of IL-6 (21.3 U/ml) when inoculated s.c. into C57BL/6 mice. The mice inoculated with FBL-3-IL-6 cells showed prolonged survival period than those inoculated with control leukemia cells. Increased cytotoxic activities of splenic NK and CTL were found in mice inoculated with FBL-3-IL-6 cells. The secretions of IL-2, TNF and GM-CSF from murine splenocytes were also found to be greatly elevated after the inoculation of FBL-3-IL-6 leukemia cells. These data suggested that transduction of IL-6 gene into FBL-3 cells magnificently decreased the tumorigenicity and increased the immunogenicity of the leukemia cells, could induce specific and nonspecific antitumor immune responses. IL-6 gene-modified leukemia cells might be of great interests to be used as vaccine for the treatment of leukemia.