[Interleukin-2 based immunotherapy of cancer]

Abstract

Interleukin-2 (IL-2) is produced by activated T-helper lymphocytes and stimulates both the antigen-specific and the non-specific immune defence. In vitro, IL-2 activated peripheral blood lymphocytes (LAK-cells) can lyse a broad spectrum of both NK-sensitive and NK-resistant tumour cell lines and IL-2 expanded tumour infiltrating lymphocytes (TIL) are, in certain cases, selectively able to lyse autologous tumour cells. In vivo, the mechanism behind the anti-tumour effect of IL-2 is unknown. Recombinant IL-2 has been available since 1984 and world-wide more than 3,000 patients have been treated. IL-2 has most frequently been administered in combination with either in vitro activated autologous effector cells and/or other cytokines or anti-cancer chemotherapeutic agents. The generation of autologous effector cells for patient treatment demands considerable resources and their contribution to the clinical effect is uncertain. The best responding tumour-types have been renal cell carcinoma and malignant melanoma with response rates up to 35% and 24%, respectively. IL-2 therapy is associated with considerable side-effects. The most serious are due to the development of a "capillary leak syndrome" with peripheral vasodilation and increased vascular permeability resulting in hypotension, oedema and organ-dysfunction. The majority of these side-effects are reversible with improvement within hours after terminating the IL-2 administration. It is concluded that IL-2 therapy is still experimental and it should be limited to treatment according to protocols in highly specialized clinical departments in a close cooperation with immunological laboratories.