Glycan array analysis of the antigen repertoire targeted by tumor-binding antibodies

Jeffrey C. Gildersleeve; Baomei Wang; Samuel Achilefu; Zhude Tu; Mai Xu

doi:10.1016/j.bmcl.2012.09.055

Glycan array analysis of the antigen repertoire targeted by tumor-binding antibodies

Jeffrey C. Gildersleeve, Baomei Wang, Samuel Achilefu, Zhude Tu, Mai Xu

Research output: Contribution to journal › Article › peer-review

16 Scopus citations

Abstract

Immunization with whole cells has been used extensively to generate monoclonal antibodies, produce protective immune responses, and discover new disease antigens. While glycans are abundant on cell surfaces, anti-glycan immune responses have not been well-characterized. We used glycan microarrays to profile 49 tumor-binding monoclonal antibodies generated by immunizing mice with whole cancer cells. A substantial proportion (41%) of the tumor binding antibodies bound carbohydrate antigens. The antibodies primarily recognize a group of 5 glycan antigens: Sialyl Lewis A (SLeA), Lewis A (LeA), Lewis X (LeX), blood group A (BG-A), and blood group H on a type 2 chain (BG-H2). The results have important implications for monoclonal antibody production and cancer vaccine development.

Original language	English (US)
Pages (from-to)	6839-6843
Number of pages	5
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	22
Issue number	22
DOIs	https://doi.org/10.1016/j.bmcl.2012.09.055
State	Published - Nov 15 2012
Externally published	Yes

Keywords

Antibody
Cancer vaccine
Carbohydrate
Glycan array
Tumor antigen

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

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10.1016/j.bmcl.2012.09.055

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title = "Glycan array analysis of the antigen repertoire targeted by tumor-binding antibodies",

abstract = "Immunization with whole cells has been used extensively to generate monoclonal antibodies, produce protective immune responses, and discover new disease antigens. While glycans are abundant on cell surfaces, anti-glycan immune responses have not been well-characterized. We used glycan microarrays to profile 49 tumor-binding monoclonal antibodies generated by immunizing mice with whole cancer cells. A substantial proportion (41%) of the tumor binding antibodies bound carbohydrate antigens. The antibodies primarily recognize a group of 5 glycan antigens: Sialyl Lewis A (SLeA), Lewis A (LeA), Lewis X (LeX), blood group A (BG-A), and blood group H on a type 2 chain (BG-H2). The results have important implications for monoclonal antibody production and cancer vaccine development.",

keywords = "Antibody, Cancer vaccine, Carbohydrate, Glycan array, Tumor antigen",

author = "Gildersleeve, {Jeffrey C.} and Baomei Wang and Samuel Achilefu and Zhude Tu and Mai Xu",

note = "Funding Information: We thank Jack Simpson (Protein Chemistry Laboratory, SAIC/NCI-Frederick) for MALDI-MS analysis of BSA conjugates. This research was supported in part by the Intramural Research Program of the NIH, NCI. ",

year = "2012",

month = nov,

day = "15",

doi = "10.1016/j.bmcl.2012.09.055",

language = "English (US)",

volume = "22",

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journal = "Bioorganic and Medicinal Chemistry Letters",

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AU - Gildersleeve, Jeffrey C.

AU - Wang, Baomei

AU - Achilefu, Samuel

AU - Tu, Zhude

AU - Xu, Mai

N1 - Funding Information: We thank Jack Simpson (Protein Chemistry Laboratory, SAIC/NCI-Frederick) for MALDI-MS analysis of BSA conjugates. This research was supported in part by the Intramural Research Program of the NIH, NCI.

PY - 2012/11/15

Y1 - 2012/11/15

N2 - Immunization with whole cells has been used extensively to generate monoclonal antibodies, produce protective immune responses, and discover new disease antigens. While glycans are abundant on cell surfaces, anti-glycan immune responses have not been well-characterized. We used glycan microarrays to profile 49 tumor-binding monoclonal antibodies generated by immunizing mice with whole cancer cells. A substantial proportion (41%) of the tumor binding antibodies bound carbohydrate antigens. The antibodies primarily recognize a group of 5 glycan antigens: Sialyl Lewis A (SLeA), Lewis A (LeA), Lewis X (LeX), blood group A (BG-A), and blood group H on a type 2 chain (BG-H2). The results have important implications for monoclonal antibody production and cancer vaccine development.

AB - Immunization with whole cells has been used extensively to generate monoclonal antibodies, produce protective immune responses, and discover new disease antigens. While glycans are abundant on cell surfaces, anti-glycan immune responses have not been well-characterized. We used glycan microarrays to profile 49 tumor-binding monoclonal antibodies generated by immunizing mice with whole cancer cells. A substantial proportion (41%) of the tumor binding antibodies bound carbohydrate antigens. The antibodies primarily recognize a group of 5 glycan antigens: Sialyl Lewis A (SLeA), Lewis A (LeA), Lewis X (LeX), blood group A (BG-A), and blood group H on a type 2 chain (BG-H2). The results have important implications for monoclonal antibody production and cancer vaccine development.

KW - Antibody

KW - Cancer vaccine

KW - Carbohydrate

KW - Glycan array

KW - Tumor antigen

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ER -

Glycan array analysis of the antigen repertoire targeted by tumor-binding antibodies

Abstract

Keywords

ASJC Scopus subject areas

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