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  • Title: Modulation of innate immunological factors by STEALTH liposome-encapsulated tumor necrosis factor-alpha in a colon tumor xenograft model.
    Author: Kim DW, Andres ML, Kajioka EH, Dutta-Roy R, Miller GM, Seynhaeve AL, ten Hagen TL, Gridley DS.
    Journal: Anticancer Res; 2002; 22(2A):777-88. PubMed ID: 12014650.
    Abstract:
    BACKGROUND: Previous studies have shown that tumor necrosis factor-alpha (TNF-alpha) encapsulated in sterically-stabilized PEGylated STEALTH liposomes (SL) can better and more safely augment the efficacy of other treatment modalities than free TNF-alpha. The aim of this study was to examine the effects of SL-TNF-alpha in the LS174T human colon tumor xenograft model and to correlate its administration with alterations in innate immune system parameters. MATERIALS AND METHODS: Nude mice (n = 128) were injected subcutaneously with LSI 74T cells and treated intravenously with SL-TNF-alpha SL-placebo, or free recombinant human TNF-alpha; the animals were euthanized at 6, 18, 36 and 96 hours after injection. RESULTS: Significant increases in leukocyte, granulocyte, monocyte and NK cell numbers were observed early (6 hours) in the blood from both SL-TNF-alpha and free TNF-alpha treated mice compared to the control group. In contrast, during the 18- to 36-hours interval, SL-TNF-alpha induced significantly higher (p<0.05) leukoctyte, T cell, and NK cell numbers, basal leukocyte proliferation, and CD25+ activation marker expression; the modulation occurred primarily in the spleen. CONCLUSION: These data indicate that both SL-TNF-alpha and free TNF-alpha can induce dramatic up-regulation in leukocyte populations early after injection. However, the up-regulation produced by SL-TNF-alpha was more prolonged and pronounced than that of TNF-alpha and had better correlation with cell activation. These findings suggest that sustained leukocyte recruitment and/or activation may be an important factor in the greater than additive or synergistic antitumor effects observed when SL-TNF-alpha is used in combination with other cancer therapies.
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