Effects of monophosphoryllipid-A on the immunization of mice with keyhole limpet hemocyanin- and muramyldipeptide-ganglioside Gfpt1 conjugates.
Since it was considered that an active immunization against ganglioside Gfpt1 (IV2Fuc-, II3NeuAc-Gg4Cer) expressed by human small cell lung cancer cells may be beneficial in the treatment of this neoplasm in humans, an optimal mode of vaccination in model mice was investigated. A novel Gfpt1-muramyldipeptide conjugate (Gfpt1-MDP) was synthesized. Its ganglioside carbohydrate-directed immunogenicity in mice as measured by serum antibody titers was comparable to that of the previously described Gfpt1-keyhole limpet hemocyanin conjugate (Gfpt1-KLH). Similar immunogenicity was displayed by free Gfpt1 in muramyldipeptide-phosphoethanolamine-containing phosphatidyl-choline, -serine (PC,PS) liposomes. Immunization with Gfpt1-vaccines in the presence of monophosphoryllipid A (MPL), in general, raised titers of anti-Gfpt1 antibodies effectively. Immunization with PC, PS-liposomes containing unconjugated Gfpt1 and MPL stimulated the highest titers observed, thereby effectively preventing tumor growth in Balbc nu/nu-mice challenged with human small cell lung cancer cells. However, there was a strong crossreaction of these and most other sera with the structurally related and widely distributed ganglioside Gtet1 (II3NeuAc-Gg4Cer). Only immunization with Gfpt1-KLH conjugate in the presence of MPL stimulated selectively high anti-Gfpt1 antibody titers showing comparably low crossreactivity to ganglioside Gtet1.
Jennemann
R
R
Abtlg. Neurochirurgie, Philipps-Universität, Marburg, Germany.
Bauer
B L
BL
Schmidt
R
R
Elsässer
H P
HP
Wiegandt
H
H
D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000818:Animals; D018288:Carcinoma, Small Cell / Q000276:immunology / Q000473:pathology; D004151:Dipeptides / Q000008:administration & dosage*; D005677:G(M1) Ganglioside / Q000008:administration & dosage / Q000031:analogs & derivatives*; D006433:Hemocyanins / Q000008:administration & dosage*; D008050:Lipid A / Q000031:analogs & derivatives* / Q000494:pharmacology; D008175:Lung Neoplasms / Q000276:immunology / Q000473:pathology; D051379:Mice; D014407:Tumor Cells, Cultured
D000276:Adjuvants, Immunologic; D004151:Dipeptides; D008050:Lipid A; D005677:G(M1) Ganglioside; C039123:fucosyl GM1 ganglioside; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin; C048436:monophosphoryl lipid A