DELIVERY OF CYTOKINES BY LIPOSOMES .2. INTERLEUKIN-2 ENCAPSULATED IN LONG-CIRCULATING STERICALLY STABILIZED LIPOSOMES - IMMUNOMODULATORY AND ANTITUMOR-ACTIVITY IN MICE

被引:40
作者
KEDAR, E [1 ]
BRAUN, E [1 ]
RUTKOWSKI, Y [1 ]
EMANUEL, N [1 ]
BARENHOLZ, Y [1 ]
机构
[1] HEBREW UNIV JERUSALEM,HADASSAH MED SCH,DEPT MEMBRANE BIOCHEM,IL-91010 JERUSALEM,ISRAEL
来源
JOURNAL OF IMMUNOTHERAPY | 1994年 / 16卷 / 02期
关键词
LIPOSOMES; INTERLEUKIN-2; PEGILATED INTERLEUKIN-2; TUMOR;
D O I
10.1097/00002371-199408000-00005
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
We have recently demonstrated that recombinant human interleukin-2 (IL-2) can be successfully encapsulated in small (mean size, 65 nm), unilamellar, long-circulating, sterically stabilized liposomes (SSL, also known as Stealth liposomes). The present study was undertaken to assess in mice the immunomodulatory and anti-tumor effects of SSL-IL-2 in comparison with soluble, unmodified IL-2 and pegilated IL-2 (PEG-IL-2). The main findings were as follows: (a) SSL-IL-2 was significantly more effective than IL-2 in increasing leukocyte number in the blood and spleen (p < 0.05) and triggering spleen lymphokine-activated killer cell activity (p < 0.01; t test). (b) In mice with advanced metastatic carcinoma previously treated with chemotherapy (cyclophosphamide), the survival was two to six times greater following administration of SSL-IL-2 as compared with IL-2 (p < 0.05; log-rank test). Moreover, successful treatment with SSL-IL-2 required lower cumulative doses (1.25 x 10(5) vs. 2.5 x 10(5) CU) and fewer (two versus five) administrations. (c) PEG-IL-2 was a more potent immunostimulator than SSL-IL-2 in normal mice and as effective therapeutically as SSL-IL-2 in tumor-bearing mice. The former agent, however, often caused marked toxicity (up to 40% mortality in some experiments), including severe thrombocytopenia. These findings suggest that SSL-IL-2 is an immunopotentiating agent superior to IL-2 in both normal mice and in tumor-bearing mice pretreated with chemotherapy.
引用
收藏
页码:115 / 124
页数:10
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