Short-duration in vitro 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 of peripherally collected mononuclear cells to high-dose human recombinant interleukin-2(rIL-2) will generate a population of pulsed lymphokine-activated killer (LAK) cells. These cells have similar cytotoxicity against natural killer cells and resistant and sensitive target cells as compared with the standard LAK cells incubated for 3-7 days with rIL-2. Therefore, the authors conducted a pilot study to investigate the activity of pulsed LAK cells in patients with advanced cancer.

METHODS

Nineteen patients were enrolled in a pilot study, and pulsed LAK cell treatment was administered two times per week for 4 weeks, followed by similar cycles if patients remained free of disease progression and unacceptable toxic effects.

RESULTS

Toxic effects consisted mainly of fever, chills, nausea, and dizziness but were self-limiting and mild. Most cycles were administered on an outpatient basis. There were six partial responses (31%), occurring in two of three patients with renal 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 melanoma and carcinoma of colon. Nine other patients had disease stabilization for 16 weeks, and two additional patients had disease progression. Phenotyping of peripheral mononuclear cells showed increases in CD56 and CD25 populations with no in vivo rIL-2 being administered after treatment with pulsed LAK cells.

CONCLUSIONS

The relative ease in generating pulsed LAK cells and the associated mild toxic effects enable prolonged stimulation of the effector cells of the patients against sensitive tumor targets, with a response rate comparable to those of high-dose rIL-2 and LAK cell treatment. Therefore, it may be a theoretically ideal adjuvant for patients with renal cell carcinoma, melanoma, and hepatoma and other applicable patients after bone marrow transplantation. The initial high response rate in patients with late-stage renal cell carcinoma and hepatocellular carcinoma indicates the need for additional confirmation.