LYMPHOKINE ACTIVATED KILLER CELL & INTERLEUKIN-2 STUDIES

LYMPHOKINE ACTIVATED KILLER CELL & INTERLEUKIN-2 STUDIES preliminary results include complete tumor regression in one patient with multiple subcutaneous metastatic melanoma, Natl. Cancer Institute Surgery Branch Chief Steven Rosenberg, MD, told the Natl. Cancer Advisory Board May 13. The patient, who began treatment with lymphokine activated killer (LAK) cells and interleukin-2 (IL-2) in November 1984, remains disease free at four months, Rosenberg reported. To date, three patients with advanced metastatic disease, in whom conventional therapies have failed, have been treated in the immunotherapy program, which uses recombinant IL-2 supplied by Cetus. A second patient with advanced rectal cancer and five pulmonary metastases has demonstrated complete regression of three of the pulmonary nodules and partial regression of the remaining two, Rosenberg reported. The patient completed a second course of therapy April 24, and investigators "suspect he is responding to their second course of therapy" based on laboratory findings, Rosenberg said. The patient's carcinoembryonic antigen dropped from 179 to 91 following the first course of treatment and has dropped from 91 to 33 since receiving the second course, he explained. A third patient with extensive melanoma has shown no response to therapy. An additional four patients are currently enrolled in the trial. Patients receive an initial administration of IL-2 for a week, which creates a drop in the number of LAK cells, Rosenberg explained. Following the discontinuance of IL-2, however, investigators find "a four-to-five fold rebound in the number of these precursor cells," at which time patients undergo leukopheresis for five days to remove circulating white blood cells. The cells are then treated with IL-2 to convert them into LAK cells, then transferred back to the patient, who also receives intravenous IL-2. The cycle is repeated a second time, for a total treatment course of six weeks. Side effects, which include fever, chills, malaise, diarrhea, fluid retention and "very mild liver function abnormalities," revert to normal "within about five to seven days after stopping IL-2 administration," he said. While emphasizing the preliminary nature of the findings, Rosenberg characterized the clinical results as "quite extraordinary." The LAK cells system "may represent the form of immunosurveillance against the transformed cell that we've been looking for for many years," he said. "The change in a tumor cell as it transforms from normal to malignant appears to be a general one recognized by lymphokine activated killer cells and there appears to be broad recognition against tumors, as well as across individuals in the ability of lymphokine activated cells to recognize tumor antigens," he said. In vitro studies with a variety of human tumor cell preparations found that 36 of 41 "were suspectible to lysis by these lymphokine activated killer or LAK cells," he reported. Tumors studied included soft tissue sarcomas; osteosarcomas; adenocarcinomas of the colon, ovary and pancreas; and a variety of lymphomas. Adoptive transfer of LAK cells "can reduce established metastases in the lung and in the liver," he said, but emphasized, "it's essential that recombinant interleukin-2 be given at the same time." Rosenberg's presentation was based on an editorial scheduled for publication in the Journal of the National Cancer Institute.