Polyethylene-glycol-modified interleukin-2 is superior to interleukin-2 in locoregional immunotherapy of established guinea-pig tumors.
Polyethylene glycol-modified recombinant human interleukin-2 (PEG-IL-2) represents a cytokine with prolonged circulatory half-life and increased antitumor activity as compared to recombinant interleukin-2 (rIL-2) after systemic administration. We studied whether PEG-IL-2 would also be advantageous in locoregional immunotherapy using a syngeneic tumor model. Intradermal inoculation of line-10 tumor cells into the flanks of strain-2 guinea-pigs results in a fast-growing tumor and regional lymph-node metastases. Treatment schedules were started on day 7 after inoculation in animals with established tumors. First, groups of 5-6 animals were treated with repeated intratumoral and perilymphatic rIL-2 or PEG-IL-2 injections. PEG-IL-2 caused significant growth inhibition of both the primary tumor and the regional lymph-node metastases at lower doses and with less frequent administration than rIL-2. The best schedule for PEG-IL-2 was 3 injections a week for 5 weeks, resulting in cure of 4/17 and 5/5 (p less than 0.01) animals at the 2 most efficient dose levels tested. Subsequent experiments indicated that the intratumoral and not the perilymphatic injection route was essential for the obtained antitumor effect. Furthermore, 12/12 animals cured after PEG-IL-2 treatment rejected a rechallenge with line-10 tumor cells, whereas no cures were seen after rIL-2 injections. PEG-IL-2 therefore appears to be a valuable substance for intratumoral immunotherapy.
Mattijssen
V
V
Department of Medicine, University Hospital, Nijmegen, The Netherlands.
Balemans
L T
LT
Steerenberg
P A
PA
De Mulder
P H
PH
D000818:Animals; D001365:Axilla; D004305:Dose-Response Relationship, Drug; D005260:Female; D006168:Guinea Pigs; D007167:Immunotherapy; D007376:Interleukin-2 / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D008198:Lymph Nodes; D008207:Lymphatic Metastasis; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000628:therapy*; D011092:Polyethylene Glycols; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use; D014407:Tumor Cells, Cultured
D007376:Interleukin-2; D011994:Recombinant Proteins; C067245:interleukin-2, polyethylene glycol-modified; D011092:Polyethylene Glycols