Polyethylene‐glycol‐modified interleukin‐2 is superior to interleukin‐2 in locoregional immunotherapy of established guinea‐pig tumors

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Abstract
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 (ρ < 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. © 1992 Wifey‐Liss, Inc.