LOCAL LOW-DOSE INTERLEUKIN-2 INDUCES SYSTEMIC IMMUNITY WHEN COMBINED WITH RADIOTHERAPY OF CANCER - A PRECLINICAL STUDY

Tumor recurrence and outgrowth of metastases limit the therapeutical e ffect of radiotherapy, We have tested whether these problems can be ov ercome by supplementing radiotherapy with locoregional interleukin-2 ( IL-2) treatment. The SL2 lymphoma and the M8013 mammary carcinoma were used. Mice bearing a 10-day-old s.c. tumor were locally irradiated an d were treated daily with IL-2 peritumorally for 5 or 10 days. Low-dos e IL-2 therapy improved local response (LR) and increased disease-free survival (DFS) in both tumor models following either single-dose irra diation or fractionated irradiation. For example, 93% of SL2-bearing m ice treated with single-dose irradiation and 10 days of IL-2 experienc ed long-term DFS, compared with 17% for irradiation alone (p < 0.0001) . Additionally, treatment of one tumor with irradiation +IL-2 led to a nti-tumor effects in a second, untreated tumor in 80% of SL2-bearing m ice. LR was increased to 100% and DFS to 70% when the second, nonirrad iated tumor was also treated with peritumoral IL-2. We conclude that s upplementing local radiotherapy with low doses of IL-2 results in incr eased local tumor control and regression of distant, non-irradiated tu mors. This type of radioimmunotherapy is a promising new approach for the clinic. (C) 1997 Wiley-Liss, Inc.