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Characterization of a mouse monoclonal IgG3 antibody to the tumor-associated globo H structure produced by immunization with a synthetic glycoconjugate

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Abstract

Globo H (Fucα1→2Galβ1→3GalNAcβ1→3Galα1→4Galβ1→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 Fucα1→2Galβ1→3GalNAcβ1→3Gal. An isomeric structure with an internal αGalNAc 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.

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Authors and Affiliations

  1. Immunology Program, New York, NY, 10021, USA

    Valery Kudryashov & Kenneth O Lloyd

  2. Clinical Immunology Service, Memorial Hospital, 1275 York Avenue, New York, NY, 10021, USA

    Govindaswami Ragupathi & Philip O Livingston

  3. Molecular Pharmacology and Therapeutics Program, Sloan-Kettering Institute, New York, NY, 10021, USA

    In Jong Kim & Samuel J Danishefsky

  4. Department of Surgery, Sahlgrenska University Hospital, Goteborg University, Goteborg, Sweden

    Michael E Breimer

Authors
  1. Valery Kudryashov
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  2. Govindaswami Ragupathi
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  3. In Jong Kim
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  4. Michael E Breimer
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  5. Samuel J Danishefsky
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  6. Philip O Livingston
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  7. Kenneth O Lloyd
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Kudryashov, V., Ragupathi, G., Kim, I.J. et al. Characterization of a mouse monoclonal IgG3 antibody to the tumor-associated globo H structure produced by immunization with a synthetic glycoconjugate. Glycoconj J 15, 243–249 (1998). https://doi.org/10.1023/A:1006992911709

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