The Immunotherapy of Human Cancer with Interleukin 2: Present Status and Future Directions

Abstract

Interleukin-2 (IL2) is the principal soluble factor responsible for the proliferation of activated T cells. In animal models and humans, administration of IL2 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. IL2 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 IL2 given by diverse routes and schedules, both alone and in combination with infusions of ex vivo IL2-activated autologour 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.