COMBINED LOCAL HYPERTHERMIA AND IMMUNOTHERAPY TREATMENT OF AN EXPERIMENTAL SUBCUTANEOUS MURINE MELANOMA

Immunotherapy (IT) has become an accepted therapeutic modality for a l imited number of tumor types. One of the limiting factors in the use o f interleukin-2 (IL-2) has been dose-related toxicity. We undertook th ese studies to study the effects of combined therapy on a murine melan oma. The B16 melanoma was implanted in the right hindlimb of C57BL/6 m ice and therapy begun on day 3 (microscopic tumor model) or day 10 (ma croscopic tumor model). Animals were divided into four groups: No ther apy, local hyperthermia (HT) alone (45 degrees C x 15 minutes on days 3 and 6 or days 10 and 13), HT + IL-2 at 300,000 IU ip tid, and HT + I L-2 at 600,000 IU ip tid. We have shown in multiple previous experimen ts that IL-2 alone at these doses has no effect on tumor growth; these groups were omitted. In the microscopic model, tumors in the no treat ment group were an average of 400 mm(2). Animals treated with HT alone had a mean tumor size of 300 mm(2). However, tumors in animals receiv ing both therapeutic modalities measured a mean of 100 mm(2) (300,000 IU IL-2 ip tid) and 80 mm(2) (600,000 IU IL-2 ip tid). In the macrosco pic tumor model, tumors in animals receiving no treatment were an aver age of 7.5 times larger than on day 10, in animals receiving HT alone were an average of 5 times larger, animals receiving IL-2 were 2.95 ti mes larger (both dose levels). These results show that combined IT + H T therapy resulted in significantly (P < .05) reduced growth with both microscopic and macroscopic tumors compared to HT alone or no therapy in a murine subcutaneous melanoma model using doses significantly low er than those usually needed to observe a therapeutic response with IL -2 used alone. This study further supports the use of this combined mo dality approach in patients with advanced malignancies. (C) 1995 Wiley -Liss, Inc.