Characterization of a mouse monoclonal IgG3 antibody to the tumor-associated globo H structure produced by immunization with a synthetic glycoconjugate.
Globo H (Fuc alpha1 --> 2Galbeta1 --> 3GalNAcbeta1 --> 3Gal alpha1 --> 4Galbeta1 --> 4Glc) is a carbohydrate structure that shows enhanced expression in many human carcinomas. From mice immunized with a globo H-KLH (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 alpha1 --> 2Galbeta1 --> 3GalNAcbeta1 --> 3Gal. An isomeric structure with an internal alphaGalNAc linkage was also recognized but less efficiently. mAb VK-9 did not react with many related structures, such as galactosylgloboside, globoside, H type 1, H type 2 blood group structures or fucosyl-gangliotetraosyl ceramide, but did react weakly with globo A ceramide. Not only did mAb VK-9 react with carbohydrate-protein conjugates but it could also recognize globo H-ceramide and human tumor cells expressing globo H. These results suggest that globo H-KLH could be explored as a vaccine in the treatment of carcinoma patients.
Kudryashov
V
V
Immunology Program, Sloan-Kettering Institute, New York, NY 10021, USA.
Ragupathi
G
G
Kim
I J
IJ
Breimer
M E
ME
Danishefsky
S J
SJ
Livingston
P O
PO
Lloyd
K O
KO
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000918:Antibody Specificity; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000737:chemistry*; D019496:Cancer Vaccines / Q000737:chemistry / Q000302:isolation & purification; D002240:Carbohydrate Sequence; D005260:Female; D006001:Glycoconjugates / Q000737:chemistry / Q000276:immunology; D006433:Hemocyanins / Q000276:immunology; D006801:Humans; D007114:Immunization; D007074:Immunoglobulin G / Q000276:immunology*; D051379:Mice; D008969:Molecular Sequence Data; D018074:Vaccines, Conjugate / Q000737:chemistry / Q000302:isolation & purification
D000911:Antibodies, Monoclonal; D015295:Antigens, Tumor-Associated, Carbohydrate; D019496:Cancer Vaccines; D006001:Glycoconjugates; D007074:Immunoglobulin G; D018074:Vaccines, Conjugate; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin