Polyethylene-glycol-modified interleukin-2 is superior to interleukin-2 in locoregional immunotherapy of established guinea-pig tumors
✍ Scribed by Vera Mattijssen; Lianne T. M. Balemans; Peter A. Steerenberg; Pieter H. M. de Mulder
- Publisher
- John Wiley and Sons
- Year
- 1992
- Tongue
- French
- Weight
- 687 KB
- Volume
- 51
- Category
- Article
- ISSN
- 0020-7136
No coin nor oath required. For personal study only.
✦ Synopsis
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 (rlL-2) after systemic administration. We studied whether PEG-IL-2 would also be advantageous in locoregional immunotherapy using a syngeneic tumor model. lntradermal inoculation of line-I0 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 rlL-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 rlL-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 < 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, I2/ I 2 animals cured after PEG-IL-2 treatment rejected a rechallenge with line-I0 tumor cells, whereas no cures were seen after rlL-2 iniections. PEG-IL-2 therefore amears to be a valuable substance for intratumoral immunothirapy.