ENHANCEMENT OF THERAPEUTIC EFFECTS OF RECOMBINANT INTERLEUKIN-2 ON A TRANSPLANTABLE RAT FIBROSARCOMA BY THE USE OF A SUSTAINED-RELEASE VEHICLE, PLURONIC GEL

  • 1 January 1987
    • journal article
    • research article
    • Vol. 47  (1) , 37-41
Abstract
We have tested the feasibility of pluronic F-127 gel (PLF-127; a polyoxyethylene-polyoxypropylene surface active block copolymer) as a sustained release vehicle for topical administration of interleukin 2 (IL-2) in order to enhance the therapeutic effects of IL-2 against a rat fibrosarcoma, KMT-17. Injection of human DNA recombinant IL-2 (3 .times. 104 units s.c.) in 30% (w/w) PLF-127 into rats provided detectable serum IL-2 levels for up to 10 h, while injection of IL-2 alone provided detectable IL-2 levels for 3 h. Whem, following s.c. inoculation with 1 .times. 105 KMT-17 tumro cells into rats, IL-2 (6 .times. 104 units/day) in PLF-17 gels was injected s.c. around the growing tumor inoculum every 2 days for 10 days from Day 1 to Day 19, the survival days of rats were more prolonged [mean survival day, 32.3 .+-. 5.4 (SD)] as compared with that of rats treated with saline [20.7 .+-. 2.1] than mean survival days of rats treated with IL-2 alone [27.3 .+-. 4.5] or PLF-127 alone [22.9 .+-. 3.3]. Moreover, the span of mean survival days of rats treated with IL-2 in PLF-127 locally (31.7 .+-. 5.9) was much longer than that of rats given IL-2 in PLF-127 systemically (22.8 .+-. 3.4). By means of a Winn assay, stronger tumor neutralizing activities were observed in regional lymph node cells obtained from tumor bearing rats treated with IL-2 in PLF-127 than were observed in lymph node cells from rats treated with IL-2 alone or PLF-127 alone (percentage of inhibition, 90.3, 12.2, and -15.5%, respectively). The therapeutic effects of IL-2 were thus found to be consistent with the antitumor activity in regional lymph node cells. These results suggest that the enhanced therapeutic effects of IL-2 in PLF-127 are due to enhancement of antitumor immune responses induced by sustained IL-2 activity at the tumor sites.

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