Local low‐dose interleukin‐2 induces systemic immunity when combined with radiotherapy of cancer. A pre‐clinical study

• Published in: International journal of cancer 1997-09, Vol.72 (6), p.1003-1007
• Main Authors: Everse, Linda A., Renes, Ingrid B., Jürgenliemk‐Schulz, Ina M., Rutgers, Derk H., Bernsen, Monique R., Dullens, Hub F.J., Den Otter, Willem, Battermann, Jan J.
• Format: Article
• Language: English
• Subjects: Animals; Antineoplastic agents; Biological and medical sciences; Combined Modality Therapy; Combined treatments (chemotherapy of immunotherapy associated with an other treatment); Disease-Free Survival; Dose Fractionation, Radiation; Female; Immunotherapy; Interleukin-2 - therapeutic use; Lymphoma - radiotherapy; Lymphoma - therapy; Mammary Neoplasms, Experimental - radiotherapy; Mammary Neoplasms, Experimental - therapy; Medical sciences; Mice; Mice, Inbred C57BL; Mice, Inbred DBA; Pharmacology. Drug treatments; Recombinant Proteins - therapeutic use
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/(SICI)1097-0215(19970917)72:6<1003::AID-IJC14>3.0.CO;2-5

Tumor recurrence and outgrowth of metastases limit the therapeutical effect of radiotherapy. We have tested whether these problems can be overcome 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 and were treated daily with IL‐2 peritumorally for 5 or 10 days. Low‐dose IL‐2 therapy improved local response (LR) and increased disease‐free survival (DFS) in both tumor models following either single‐dose irradiation or fractionated irradiation. For example, 93% of SL2‐bearing mice treated with single‐dose irradiation and 10 days of IL‐2 experienced long‐term DFS, compared with 17% for irradiation alone (p < 0.0001). Additionally, treatment of one tumor with irradiation +IL‐2 led to anti‐tumor effects in a second, untreated tumor in 80% of SL2‐bearing mice. LR was increased to 100% and DFS to 70% when the second, non‐irradiated tumor was also treated with peritumoral IL‐2. We conclude that supplementing local radiotherapy with low doses of IL‐2 results in increased local tumor control and regression of distant, non‐irradiated tumors. This type of radioimmunotherapy is a promising new approach for the clinic. Int. J. Cancer 72:1003–1007, 1997. © 1997 Wiley‐Liss, Inc.