Use of mannosylated cationic liposomes/ immunostimulatory CpG DNA complex for effective inhibition of peritoneal dissemination in mice.

Abstract

BACKGROUND:

Immunotherapy using immunostimulatory CpG DNA could be a promising new therapeutic approach to combat refractory peritoneal dissemination. In the present study, we report the use of a mannosylated cationic liposomes/immunostimulatory CpG DNA complex (Man/CpG DNA lipoplex) for effective inhibition of peritoneal dissemination in mice.

METHODS:

The immune response characteristics of the Man/CpG DNA lipoplex were evaluated by measuring tumor necrosis factor (TNF)-alpha production using primary cultured mouse peritoneal macrophages. Subsequently, Man/CpG DNA lipoplex was administered intraperitoneally (i.p.) to peritoneal dissemination model mice, and the number of tumor cells (colon26/Luc) was quantitatively evaluated by measuring luciferase activity. The effect on survival time of the Man/CpG DNA lipoplex was also investigated. The serum transaminase levels of mice receiving i.p. Man/CpG DNA lipoplex treatment were measured to evaluate systemic toxicity.

RESULTS:

The Man/CpG DNA lipoplex induced higher TNF-alpha production from macrophages than CpG DNA complexed with conventional cationic liposomes and galactosylated cationic liposomes (Bare/CpG DNA lipoplex and Gal/CpG DNA lipoplex), suggesting mannose receptor-mediated CpG DNA transfer. Intraperitoneal administration of Man/CpG DNA lipoplex inhibited the proliferation of tumor cells in the greater omentum and the mesentery more efficiently than Bare/CpG DNA lipoplex and Gal/CpG DNA lipoplex. Furthermore, the survival time of the peritoneal dissemination model mice was prolonged by i.p. administration of Man/CpG DNA lipoplex. The serum transaminase levels of mice receiving i.p. Man/CpG DNA lipoplex were found to be the same as those of untreated mice.

CONCLUSIONS:

The results obtained suggest that i.p. administered Man/CpG DNA lipoplex can be used for efficient immunotherapy to combat peritoneal dissemination.

• Authors: Yukari Kuramoto, Shigeru Kawakami, Shuwen Zhou, Kyouichi Fukuda, Fumiyoshi Yamashita, Mitsuru Hashida
• Journal: The journal of gene medicine (J Gene Med) Vol. 10 Issue 4 Pg. 392-9 (Apr 2008) ISSN: 1521-2254 [Electronic] England
• PMID: 18181219 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: (c) 2008 John Wiley & Sons, Ltd.

Chemical References

• Tumor Necrosis Factor-alpha
• Interleukin-10
• DNA

Topics

• Animals
• Cell Line, Tumor
• DNA (therapeutic use)
• Female
• Immunotherapy
• Interleukin-10 (biosynthesis)
• Macrophages, Peritoneal (drug effects, immunology)
• Male
• Mice
• Mice, Inbred BALB C
• Mice, Inbred ICR
• Particle Size
• Peritoneal Neoplasms (drug therapy, secondary)
• Tumor Necrosis Factor-alpha (biosynthesis)