Perilymphatic injections of cytokines: a new tool in active cancer immunotherapy. Experimental rationale and clinical findings.

Various strategies for local immunotherapy performed by using lymphokines and lymphocytes are presented. In experimental mice models, the antitumor reaction elicited through the injection of little amounts of IL-2 and gamma-IFN at the tumor growth site is significantly enhanced by the concurrence of lymphocytes from tumor bearing mice artificially admixed to challenging tumor cells. These lymphocytes act as initiator or helper cells that elicit both a local and a systemic long lasting immune reaction by the release of additional lymphokines. The reaction activated mostly involves draining lymph nodes, where multiple reaction mechanisms are induced. The local injection of cocktails of molecularly defined lymphokines can also mimic the helper action of lymphocytes and trigger a similarly effective anti-tumor reaction. A set of pilot clinical trials with IL-2 or gamma-IFN injected perilymphatically were initiated in patients with advanced primary or recurrent localized tumors of the head and neck and the bladder. This treatment appears to elicit a local reaction by activating a few pathways of patients immunoreactivity, whose efficiency may well be high, as shown by the tumor inhibition often observed.