In Vivo Enhancement of Antitumor Immunity by Interleukin 2-rich Lymphokines

The ability of interleukin 2 (IL-2) to enhance in vivo antitumor immunity has been evaluated in the line 1 alveolar cell carcinoma (L1) model of BALB/c mice. A crude supernatant from phorbol myristate acetate exposed EL-4 cells rich in IL-2 plus other lymphokines (EL-4 IL-2), a concanavalin A-induced supernatant from murine splenocytes (Con A IL-2), and recombinant IL-2 (rIL-2) provided by Biogen were tested. Mice were immunized with a cloned population of L1 cells (106 irradiated L1 cells given s.c. in the left inguinal region) followed by s.c. injections of EL-4 IL-2, Con A IL-2, or rIL-2 given to the same site. Two immunizations of L1 cells each followed by IL-2 administration were given prior to challenge with live L1 cells s.c. on the right chest wall. Mice receiving EL-4 IL-2 survived significantly longer than those receiving L1 cells only. Daily administration of EL-4 IL-2 for 7 days after the last L1 immunization was significantly better than 3 days ( P < 0.01) which in turn was significantly better than 1 day ( P < 0.05). Among the doses tested (normalized in vitro to the Biologic Response Modifiers Program IL-2 standard) 404 units of IL-2/injection was optimal. The EL-4 IL-2 had to be injected adjacent to the site of L1 cells; s.c. injection at a distant site or i.p. was not effective. When rIL-2 or Con A IL-2 was substituted for EL-4 IL-2, survival was not prolonged; however, if Con A IL-2 (low IL-2 levels) was supplemented with rIL-2 to 404 units of IL-2, it augmented immunity as well as 404 units of EL-4 IL-2. The data suggest that IL-2 is not the only lymphokine active in augmenting antitumor immunity induced by L1 cells. Some preliminary experiments indicate that a multilymphokine approach may have potential clinical relevance.