CHARACTERIZATION OF A MOUSE MONOCLONAL IGG3 ANTIBODY TO THE TUMOR-ASSOCIATED GLOBO-H STRUCTURE PRODUCED BY IMMUNIZATION WITH A SYNTHETIC GLYCOCONJUGATE

Globo H (Fuc alpha 1-->2Gal beta 1-->3GalNAc beta 1-->3Gal alpha 1-->4 Gal beta 1-->4Glc) is a carbohydrate structure that shows enhanced exp ression in many human carcinomas. From mice immunized with a globo H-K LH (keyhole limpet hemocyanin) synthetic conjugate an IgG3 monoclonal antibody (mAb VK-9) was derived that recognizes the globo H structure. Serological analysis showed that the minimal structure recognized by this mAb was the tetrasaccharide sequence Fuc alpha 1-->2Gal beta 1--> 3Gal-NAc beta 1-->3Gal. An isomeric structure with an internal alpha G alNAc linkage was also recognized but less efficiently. mAb VK-9 did n ot react with many related structures, such as galactosylgloboside, gl oboside, H type 1, H type 2 blood group structures or fucosyl-gangliot etraosyl ceramide, but did react weakly with globo A ceramide. Not onl y did mAb VK-9 react with carbohydrate-protein conjugates but it could also recognize globo H-ceramide and human tumor cells expressing glob o H. These results suggest that globo H-KLH could be explored as a vac cine in the treatment of carcinoma patients.