THE ANTITUMOR EFFECT INDUCED BY LOCAL INJECTIONS WITH INTERLEUKIN-2 IS DIMINISHED BY COMBING WITH A LOCAL INJECTION WITH MITOMYCIN-C

We investigated the antitumor effect of local injections with interleu kin (IL)-2 in combination with an injection with mitomycin C (MMC). In BALB/c mice inoculated intraperitoneally (i.p.) with syngeneic Meth A fibrosarcoma on day 0, the i.p. injections with IL-2 at a dose of 200 00U twice daily from day 7 to day 10 significantly prolonged survival of the treated mice and such treatment augmented a concomitant immunit y specific for the tumor i.p. inoculated. On the other hand, the i.p. injections with IL-2 at a dose of either 5000U or 50000U resulted in n o prolonged survival of the treated mice. In addition, neither intrave nous nor subcutaneous injections with IL-2 at a dose of 20000U showed the prolonged survival of the treated mice. We further investigated a modulatory effect of a local injection with MMC on the IL-2-induced an titumor effect. The in vivo antitumor effect of local injections with IL-2 was not detected when combined with a local administration of MMC , whereas a systemic administration of MMC showed no such inhibitory e ffect on the IL-2-induced antitumor effect. Moreover, a delayed-type h ypersensitivity response against Meth A, which was augmented by the lo cal injections with IL-2, was significantly diminished by the local ad ministration of MMC. Collectively, our results indicate that local inj ections with IL-2, could elicit the antitumor effect in vivo only when given at an optimal dose and that this effect could be rather diminis hed by combing with a local administration of MMC.