Adoptive Immunotherapy of Human Cancer Using Low-Dose Recombinant Inter leukin 2 and Lymphokine-activated Killer Cells1

The adoptive transfer of recombinant-methionyl human interleukin 2 (rIL-2)-activated autologous peripheral blood mononuclear lymphokineactivated killer (LAK) cells to cancer patients is being evaluated as an alternative to conventional cancer therapy. We have independently de veloped an alternative regimen to previously reported adoptive ¡niiminotherapy protocols using rIL-2 and LAK cells which features the prolonged administration of low-dose rIL-2 (30,000 units/kg) and an automated, entirely enclosed system of peripheral blood cell procurement, culture, harvest, and reinfusion of activated cells. The cell culture system was tested with a murine tumor model in which LAK cells generated in plastic culture bags were reinfused into tumor-bearing mice. Tumor regression was as effective with cells activated ¡nthe bags as in conventional culture flasks. Twenty-eight cancer patients were treated for 5 consecutive days with low-dose rIL-2, followed by leukapheresis, infusion of LAK cells, and prolonged IL-2 administration. At least 50% tumor regression was observed in 46% of all patients treated. These data imply that human peripheral blood mononuclear cells retain fully their capacity for rIL-2induced activation and effector cell function under this alternative ap proach, and further, that a low-dose rIL-2 regimen with markedly reduced toxicities can be as effective as high-dose rIL-2 regimens if low-dose rlL2 is given for a prolonged period of time following LAK cell infusion.