IMMUNOGENICITY OF SYNTHETIC CONJUGATES OF LEWIS(Y) OLIGOSACCHARIDE WITH PROTEINS IN MICE - TOWARDS THE DESIGN OF ANTICANCER VACCINES

Many human carcinomas overexpress the Lewis(y) (Le(y)) blood-group epi tope [Fuc alpha 1-->Gal beta 1-->4 (Fuc alpha 1-->3)GlcNAc beta 1-->3G al-]. With a view to developing Leu based vaccines we have examined th e immunogenicity of Le(y)-protein conjugates in mice. Leu pentasacchar ide was synthesized as its allyl glycoside and coupled to keyhole limp er hemocyanin (KLH) by reductive amination or by a novel method utiliz ing a maleido-derivitized alkyl carboxyhydrazide as a bridging group t o 2-iminothiolane-derivitized KLH. Le(y) oligosaccharide was also coup led to bovine serum albumin by reductive amination. Immunization of gr oups of mice with the three conjugates, together with the immunologica l adjuvant QS21, showed that Le(y) oligosaccharide directly coupled to KLH was the most efficient conjugate for eliciting IgG and IgM antibo dy responses to naturally occurring forms of Le(y) epitopes carried on mucins and glycolipids. These antibodies were also reactive with and cytotoxic to a human breast cancer cell line expressing Le(y) (MCF-7). These experiments suggest that Le(y)-KLH antigen and QS21 adjuvant co uld be considered as an immunogenic therapeutic vaccine in carcinoma p atients.