THE IMMUNOTHERAPY OF HUMAN CANCER WITH INTERLEUKIN-2 - PRESENT STATUS AND FUTURE-DIRECTIONS

Interleukin-2 (IL-2) is the principal soluble factor responsible for the proliferation of activated T cells. In animal models and humans, administration of IL-2 can induce regressions of established cancers. These antitumor effects may be partially mediated by cytotoxic effector cells activated by IL-2, including lymphokine-activated killer (LAK) cells and cytotoxic T lymphocytes. IL-2 has additional effects on other components of the cellular immune system, including B cells and macrophages, and induces secretion of other soluble mediators, including tumor necrosis factors (TNF) alpha and beta, and interferon-gamma. These effects may contribute to the antitumor activity of IL-2 as well as its dose-related toxicity. Multiple Phase I and II trials have been completed or are ongoing evaluating the clinical and biological effects of IL-2 given by diverse routes and schedules, both alone and in combination with infusions of ex vivo IL-2-activated autologous LAK cells. Other studies have begun to explore the potential for antitumor synergy when IL-2 is combined with the different interferons, TNF, monoclonal antibodies, and cytotoxic drugs. The biology, toxicity, and clinical activity documented in IL-2 clinical trials to date are reviewed, and prospects for future directions outlined.