Local low-dose interleukin-2 induces systemic immunity when combined with radiotherapy of cancer. A pre-clinical study.
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.
Everse
L A
LA
Department of Radiotherapy, Academic Hospital, Utrecht, The Netherlands. dgk.oncologie@pobox.ruu.nl
Renes
I B
IB
Jürgenliemk-Schulz
I M
IM
Rutgers
D H
DH
Bernsen
M R
MR
Dullens
H F
HF
Den Otter
W
W
Battermann
J J
JJ
D000818:Animals; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D019583:Dose Fractionation, Radiation; D005260:Female; D007167:Immunotherapy; D007376:Interleukin-2 / Q000627:therapeutic use*; D008223:Lymphoma / Q000532:radiotherapy / Q000628:therapy*; D008325:Mammary Neoplasms, Experimental / Q000532:radiotherapy / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D011994:Recombinant Proteins / Q000627:therapeutic use
D007376:Interleukin-2; D011994:Recombinant Proteins