ANTITUMOR 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 admi nistration on murine syngeneic tumors, Meth A fibrosarcoma, MH134 hepa toma and Lewis lung (LL) carcinoma. The latter two tumors are known to be relatively low in immunogenicity, highly metastatic and to have lo w sensitivity to biological response modifiers. Although the intraderm al administration of LPSp had a significantly suppressive effect on th e growth of all tumors, including seventy-five percent of complete reg ression of mice bearing Meth A tumor, no complete regression was obser ved in MH134 ol LL tumors. In combination with cyclophosphamide given once prior to the administration of LPS, however, the antitumor effect s by intradermal administration of LPS were significantly augmented an d there was complete regression in all types of tumors. Pretreatment b y anti-tumor necrosis factor antibody reduced the effect exerted by LP S, suggesting that induced tumor necrosis factor might have a crucial role. Toxicity of intradermal administration of LPS was 230 similar to 380 times less than that by the intravenous route. Thus clinical appl ication of LPS administered intradermally in combination with chemothe rapeutics such as cyclophosphamide appeals promising in terms of its a ntitumor effect as well as toxicity.