lipid-a and Carcinoma--Small-Cell

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.

Topics: Adjuvants, Immunologic; Animals; Carcinoma, Small Cell; Dipeptides; G(M1) Ganglioside; Hemocyanins; Lipid A; Lung Neoplasms; Mice; Tumor Cells, Cultured