SHORT-DURATION INVITRO INTERLEUKIN-2-ACTIVATED MONONUCLEAR-CELLS FOR ADVANCED CANCER - A HONG-KONG BIOTHERAPY PILOT-STUDY TRIAL

Background. In vitro studies have demonstrated that a brief exposure o f peripherally collected mononuclear cells to high-dose human recombin ant interleukin-2 (rIL-2) will generate a population of pulsed lymphok ine-activated killer (LAK) cells. These cells have similar cytotoxicit y against natural killer cells and resistant and sensitive target cell s as compared with the standard LAK cells incubated for 3-7 days with rIL-2. Therefore, the authors conducted a pilot study to investigate t he activity of pulsed LAK cells in patients with advanced cancer. Meth ods. Nineteen patients were enrolled in a pilot study, and pulsed LAK cell treatment was administered two times per week for 4 weeks, follow ed by similar cycles if patients remained free of disease progression and unacceptable toxic effects. Results. Toxic effects consisted mainl y of fever, chills, nausea, and dizziness but were self-limiting and m ild. Most cycles were administered on an outpatient basis. There were six partial responses (31%), occurring in two of three patients with r enal cell carcinoma, two of four with hepatocellular carcinoma, one of seven with non-small cell lung carcinoma, and one of one with ovarian carcinoma. Two minimal responses were seen in one case each of melano ma and carcinoma of colon. Nine other patients had disease stabilizati on for 16 weeks, and two additional patients had disease progression. Pheno-typing of peripheral mononuclear cells showed increases in CD56 and CD25 populations with no in vivo rIL-2 being administered after tr eatment with pulsed LAK cells. Conclusions. The relative ease in gener ating pulsed LAK cells and the associated mild toxic effects enable pr olonged stimulation of the effector cells of the patients against sens itive tumor targets, with a response rate comparable to those of high- dose rIL-2 and LAK cell treatment. Therefore, it may be a theoreticall y ideal adjuvant for patients with renal cell carcinoma, melanoma, and hepatoma and other applicable patients after bone marrow transplantat ion. The initial high response rate in patients with late-stage renal cell carcinoma and hepatocellular carcinoma indicates the need for add itional confirmation.