Flavone-8-acetic acid augments systemic natural killer cell activity and synergizes with IL-2 for treatment of murine renal cancer.
The investigational drug flavone-8-acetic acid (FAA) potently augments NK activity in the spleen, liver, lungs, and peritoneum in a dose-dependent manner after i.v. or i.p. administration. Augmented NK activity peaks by 24 h after FAA injection and returns to normal after 6 days. Combined treatment of established murine renal cancer with FAA and rIL-2 results in up to 80% long term survival whereas FAA or rIL-2 alone were unable to induce any long term survivors. The optimal dose of rIL-2 required for use with FAA was in the range of 10,000 to 30,000 U/day. Further studies demonstrated that the regimen of FAA plus rIL-2 administration that was effective in treating established murine renal cancer also induced a more potent augmentation of NK activity than did either FAA or rIL-2 alone. Subsequent studies revealed that the therapeutic effectiveness of FAA plus rIL-2 was significantly reduced when tumor-bearing mice were treated with anti-asialo GM1 serum. These results are consistent with a role for augmented NK activity in the therapeutic effects of FAA plus rIL-2 murine renal cancer. In addition, these studies demonstrate that FAA and rIL-2 is a useful approach for cancer treatment in that subtoxic doses of rIL-2 can be used and significant anti-tumor efficacy occurs even without accompanying adoptive immunotherapy.
Wiltrout
R H
RH
Laboratory of Experimental Immunology, National Cancer Institute-Frederick Cancer Research Facility.
Boyd
M R
MR
Back
T C
TC
Salup
R R
RR
Arthur
J A
JA
Hornung
R L
RL
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D004357:Drug Synergism; D005419:Flavonoids / Q000008:administration & dosage*; D005677:G(M1) Ganglioside; D006028:Glycosphingolipids / Q000502:physiology; D007113:Immunity, Innate / Q000187:drug effects; D007167:Immunotherapy; D007376:Interleukin-2 / Q000008:administration & dosage*; D007680:Kidney Neoplasms / Q000628:therapy*; D007694:Killer Cells, Natural / Q000276:immunology*; D051379:Mice
D000970:Antineoplastic Agents; D005419:Flavonoids; D006028:Glycosphingolipids; D007376:Interleukin-2; D005677:G(M1) Ganglioside; C018835:asialo GM1 ganglioside; C049328:flavone acetic acid