Antitumor and antimicrobial activities of lipid A-subunit analogue GLA-27.
Activities for enhancing nonspecific host resistance against microbial infections and growth inhibition against tumors by a lipid A-subunit analogue GLA-27 were investigated. GLA-27, a 4-O-phosphono-D-glucosamine derivative with 2-N-3-tetradecanoyloxytetradecanoyl and 3-O-tetradecanoyl group, inhibited significantly the growth of solid-type tumors RL male 1 lymphoma and Meth A fibrosarcoma. In the case of RL male 1 lymphoma, 2.5 micrograms of GLA-27 was needed to exhibit the activity, while for Meth A fibrosarcoma, 250 micrograms of GLA-27 was needed. On the other hand, tail lesions induced by intravenous inoculation with vaccinia virus were effectively suppressed in mice injected with 1 microgram of GLA-27 1 day before the viral injection. The antiviral activity of GLA-27 was 100 times higher than that of MDP by ED50. GLA-27 also showed nonspecific protective activity against Pseudomonas aeruginosa infection at a dose of 30 micrograms/mouse, although the activity was far less than that induced by lipid A. GLA-27 did not exhibit toxic activities such as pyrogenicity and Shwartzman reaction.
Nakatsuka
M
M
Kitasato Institute, Tokyo, Japan.
Kumazawa
Y
Y
Ikeda
S
S
Yamamoto
A
A
Nishimura
C
C
Homma
J Y
JY
Kiso
M
M
Hasegawa
A
A
D000276:Adjuvants, Immunologic; D000818:Animals; D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents; D000998:Antiviral Agents; D004353:Drug Evaluation, Preclinical; D008050:Lipid A / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009374:Neoplasms, Experimental / Q000188:drug therapy; D011552:Pseudomonas Infections / Q000188:drug therapy; D014615:Vaccinia / Q000188:drug therapy
D000276:Adjuvants, Immunologic; D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents; D000998:Antiviral Agents; D008050:Lipid A; C048988:GLA 27