Anti-tumor effect of lipopolysaccharide by intradermal administration as a novel drug delivery system.
We examined the antitumor effect of lipopolysaccharide extracted from Pantoea agglomerans, a Gram-negative bacterium, using intradermal administration on murine syngeneic tumors, Meth A fibrosarcoma, MH134 hepatoma and Lewis lung (LL) carcinoma. The latter two tumors are known to be relatively low in immunogenicity, highly metastatic and to have low sensitivity to biological response modifiers. Although the intradermal administration of LPSp had a significantly suppressive effect on the growth of all tumors, including seventy-five percent of complete regression of mice bearing Meth A tumor, no complete regression was observed in MH134 or LL tumors. In combination with cyclophosphamide given once prior to the administration of LPS, however, the antitumor effects by intradermal administration of LPS were significantly augmented and there was complete regression in all types of tumors. Pretreatment by anti-tumor necrosis factor antibody reduced the effect exerted by LPS, suggesting that induced tumor necrosis factor might have a crucial role. Toxicity of intradermal administration of LPS was 230-380 times less than that by the intravenous route. Thus clinical application of LPS administered intradermally in combination with chemotherapeutics such as cyclophosphamide appears promising in terms of its antitumor effect as well as toxicity.
Inagawa
H
H
Department of Molecular Medicine, Takano Hospital, Kumamoto, Japan.
Nishizawa
T
T
Noguchi
K
K
Minamimura
M
M
Takagi
K
K
Goto
S
S
Soma
G
G
Mizuno
D
D
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use* / Q000633:toxicity; D016503:Drug Delivery Systems; D004755:Enterobacteriaceae; D005260:Female; D005354:Fibrosarcoma / Q000188:drug therapy* / Q000473:pathology; D007271:Injections, Intradermal; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000627:therapeutic use* / Q000633:toxicity; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D000970:Antineoplastic Agents; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha