Lymphokine-activated tumor inhibition: Combinatory activity of a synthetic nonapeptide from interleukin-1, interleukin-2, interleukin-4, and interferon-γ injected around tumor-draining lymph nodes

This report initially reviews the progressive steps of research designed to build up a new, well-defined helper system triggering both the non-specific and the tumor-specific immune reactivity of a host bearing a tumor, in order to impair tumor growth. Tumor-specific T-helper lymphocytes were first generated in vitro from the spleen of mice with evident tumors. As these lymphocytes inhibit tumor growth by recruiting host reactivity through the release of lymphokines, the peri-tumoral injection of interleukin-2 (IL-2) was then experimented. Repeated injections of 10 units of IL-2 are only weakly effective, but its triggering of an efficient anti-tumor reactivity is markedly enhanced when non-reactive lymphocytes directly obtained from tumor-bearing mice are artificially admixed with the challenge tumor cells. Lastly, in order to ascertain whether lymphocytes themselves could be dispensed with, lymphokines were injected around tumor-draining lymph nodes. Ten daily injections of I pg of the 163-171 synthetic nonapeptide of human IL-1 β appeared very efficient in activating tumor inhibition, particularly when combined with IL-4 or (to a lesser extent) IL-2.