[Immunotherapy: current problems and outlook].

Abstract

Cytokines are soluble mediators involved in cell-cell regulations in the immunological and the hematopoietic systems-genetic engineering now allows the characterization and the availability of recombinant molecules, some of them being recently introduced in clinical trials. Interleukin-2 (IL-2) is the first factor having demonstrated a reproducible therapeutic effect on human metastatic solid tumors, mainly chemo-resistant. High-dose IL-2 alone could achieve about 25% objective responses in metastatic renal cancers, with a low but significant number of complete, relatively long-lasting complete responses. Similar data are obtained in metastatic melanoma. IL-2 is probably acting through the activation of cytotoxic lymphocytes (LAK: lymphokine activated killers). The interest for simultaneous administration of autologous LAK cells generated through in vitro culture with IL-2 is discussed. Cytokine therapy is currently limited by important systemic toxicities, including mainly general symptoms with fever, and a capillary leak syndrome with weight gain, edema and functional renal failure-cardiac are respiratory troubles can be life-threatening. Future trends for cytokine therapy will be: The discovery of new cytokines, and a better knowledge of their synergies, allowing the design of rational associations. A letter understanding of the mechanisms of toxicities, allowing specific prevention of adverse effects not needed for efficient anti-tumor action. Gene therapy, which will lead to important and prolonged release of cytokines by the tumor cells themselves, or by infiltrating peri-tumoral cells, in order to achieve local efficacy and to circumvent systemic toxicities.