[Principles of treatment with cells called "LAK" cells]

A novel approach for immunotherapy of cancer is presently under investigation. This treatment initially developed by Steven Rosenberg and colleagues is based on both the transfusion of autologous lymphocytes preactivated in vitro using interleukin 2 and the simultaneous infusion of the lymphokine in vivo. The two major limiting factors for these new protocols are, on the one hand, the heavy infrastructure necessary for in vitro cell treatment, and, on the other hand, the dose-dependent toxicity of IL2 infusions. Results of clinical trials are still preliminary; they suggest that the therapy may be of interest in melanomas and renal cell carcinomas. However, only a minority of patients with these relatively susceptible tumors display substantial responses. Thus, the protocols need to be improved which makes it critical to understand the biological mechanisms underlying tumor regression in vivo. The dominant working hypothesis is that IL2 enhances firstly in vitro and then in vivo the activity of certain lymphocytes able to destroy tumor cells via a direct cytotoxic effect. This view supported by murine experimental models remains to be demonstrated in the human. One way of testing it, is to infuse highly purified fractions of killer lymphocytes instead of the whole peripheral blood suspensions that are used presently. We are attempting to develop this approach and a trial is presently beginning at the Gustave-Roussy Institute in a series of patients with renal cell carcinoma.