| First Author | Yamanaka K | Year | 1999 |
| Journal | Cancer Immunol Immunother | Volume | 48 |
| Issue | 6 | Pages | 297-302 |
| PubMed ID | 10473804 | Mgi Jnum | J:57640 |
| Mgi Id | MGI:1345034 | Doi | 10.1007/s002620050578 |
| Citation | Yamanaka K, et al. (1999) Synergistic antitumor effects of interleukin-12 gene transfer and systemic administration of interleukin-18 in a mouse bladder cancer model. Cancer Immunol Immunother 48(6):297-302 |
| abstractText | We introduced the interleukin-12 (IL-12) gene into the mouse bladder cancer cell line (MBT2) to establish sublines that secrete bioactive IL-12. IL-12-secreting MBT2 (MBT2/IL-12) sublines were completely rejected when subcutaneously implanted into immunocompetent syngeneic C3H mice. Although this antitumor effect did not change when IL-12-secreting cells were injected into immunodeficient mice whose CD8(+) T or CD4(+) T cells had been depleted by the corresponding antibody, it was abrogated when natural killer cells were depleted by anti-asialoGM1 antibody. In addition, when parental MBT2 cells mixed with MBT2/IL-12 cells were subcutaneously injected into mice, admixed MBT2/IL-12 inhibited the growth of the parental tumor. Furthermore, this antitumor effect was enhanced by systemic IL-18 administration. This synergism was abrogated when the mice were treated with interferon-gamma-neutralizing antibody in vivo. In conclusion, local secretion of IL-12 led to effective antitumor activity that was enhanced by systemic administration of IL-18. Interferon-gamma plays an important role in the synergism of IL-12 gene transduction and systemic administration of IL-18. |
