EFFECTS OF MONOPHOSPHORYLLIPID-A ON THE IMMUNIZATION OF MICE WITH KEYHOLE LIMPET HEMOCYANIN-GANGLIOSIDE AND MURAMYLDIPEPTIDE-GANGLIOSIDE GFPT1 CONJUGATES

Since it was considered that an active immunization against gangliosid e Gfpt1 (IV(2)Fuc-, II(3)NeuAc-Gg(4)Cer) 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 investiga ted. A novel Gfpt1-muramyldipeptide conjugate (Gfpt1-MDP) was synthesi zed, Its ganglioside carbohydrate-directed immunogenicity in mice as m easured by serum antibody titers was comparable to that of the previou sly described Gfpt1-keyhole limpet hemocyanin conjugate (Gfpt1-KLH). S imilar immunogenicity was displayed by free Gfpt1 in muramyldipeptide- phosphoethanolamine-containing phosphatidyl-choline, -serine (PC, PS) liposomes. Immunization with Gfpt1-vaccines in the presence of monopho sphoryllipid A (MPL), in general, raised titers of anti-Gfpt1 antibodi es effectively, Immunization with PC, PS-liposomes containing unconjug ated Gfpt1 and MPL stimulated the highest titers observed, thereby eff ectively preventing tumor growth in Balbc nu/nu-mice challenged with h uman small cell lung cancer cells, However, there was a strong crossre action of these and most other sera with the structurally related and widely distributed ganglioside Gtet1 (II(3)NeuAc-Gg(4)Cer). Only immun ization with Gfpt1-KLH conjugate in the presence of MPL stimulated sel ectively high anti-Gfpt1 antibody titers showing comparably low crossr eactivity to ganglioside Gtet1.