Successful in Vivo Generation of Canine Lymphokine-Activated Killer Cells by Continuous Recombinant Interleukin-2 Infusion through the Splenic Artery

Abstract

We studied the efficacy of infusing human recombinant interleukin-2 (IL-2) through the splenic artery for generation of lynphokine activated killer (LAK) cells in vivo in a canine system. Catheters were inserted into the splenic artery, portal vein and inferior vena cava (IVC) in Beagle dogs. IL-2 was administered continuously through either the splenic artery or IVC by portable infusion pump and the cytotoxic activity of portal vein blood lymphocytes (PVBL) and peripheral blood lymphocytes (PBL) against canine osteosarcoma D-17 target cells was monitored. Following administration low-dose IL-2 (8x10⁵ IU/day) for 6 days through the splenic artery, LAK precursor cells were present, but not following administration intravenously. Interestingly, when a high dose of IL-2 (4x10⁶ IU/day on days 1-6 and 13-18) was administered through the splenic artery, strong cytotoxicity was detected in PVBL and PBL without subsequent culture in vitro with IL-2, suggesting that an infusion rate of 4x10⁶IU/day IL-2 may be sufficient for generation of LAK cells in vivo. These results suggest that continuous infusion of IL-2 through the splenic artery can generate LAK cells more easily and may prove especially useful for the immunotherapy of hepatic micrometastasis.