Comparison of antigen constructs and carrier molecules for augmenting the immunogenicity of the monosaccharide epithelial cancer antigen Tn Journal Article

  


Authors: Kagan, E.; Ragupathi, G.; Yi, S. S.; Reis, C. A.; Gildersleeve, J.; Kahne, D.; Clausen, H.; Danishefsky, S. J.; Livingston, P. O.
Article Title: Comparison of antigen constructs and carrier molecules for augmenting the immunogenicity of the monosaccharide epithelial cancer antigen Tn
Abstract: We have demonstrated previously that the optimal method for inducing an antibody response against defined cancer antigens is covalent conjugation of the antigen to keyhole limpet hemocyanin (KLH) and use of the potent saponin adjuvant QS-21. Single molecules of glycolipids (tetrasaccharides, pentasaccharides, or hexasaccharides) and MUC1 peptides (containing between one and five MUC1 tandem repeats) conjugated to KLH have proven sufficient for antibody recognition and vaccine construction. However, cancer specificity of monoclonal antibodies against the monosaccharide Tn and disaccharide sTn comes largely from recognition of clusters (c) of these molecules on the cell surface. Tn consists of a monosaccharide (GalNAc) O-linked to serine or threonine on epithelial cancer mucins which are uniquely rich in serines and threonines. We test here several Tn constructs: Tn monosaccharide, Tn(c) prepared on a triple threonine backbone, and Tn prepared on a partially or fully glycosylated MUC1 backbone. We determine that Tn(c) is more effective than Tn, and conjugation to KLH is more effective than conjugation to BSA or polystyrene beads for inducing ELISA reactivity against Tn, and FACS reactivity against Tn-positive tumor cells. Surprisingly, MUC1 glycosylated with Tn at three or five sites per 20 amino acid MUC1 tandem repeat and conjugated to KLH, induced the strongest antibody response against Tn and tumor cells expressing Tn, and had the additional advantage of inducing antibodies against MUC1. © Springer-Verlag 2004.
Keywords: controlled study; human cell; nonhuman; comparative study; flow cytometry; mouse; animals; mice; animal experiment; cell line, tumor; drug synthesis; immunoreactivity; enzyme linked immunosorbent assay; mice, inbred c57bl; cancer vaccine; cancer vaccines; immunogenicity; antibody response; tumor cell; carcinoma; glycosylation; threonine; bovine serum albumin; mucin 1; enzyme-linked immunosorbent assay; polystyrene; fluorescence activated cell sorting; antibodies, neoplasm; antigens, tumor-associated, carbohydrate; tn antigen; keyhole limpet hemocyanin; hemocyanin; vaccines, conjugate; conjugate vaccine; tandem repeat; microspheres; ca-15-3 antigen; monosaccharide; muc1; glycosylated muc1
Journal Title: Cancer Immunology, Immunotherapy
Volume: 54
Issue: 5
ISSN: 0340-7004
Publisher: Springer  
Date Published: 2005-05-01
Start Page: 424
End Page: 430
Language: English
DOI: 10.1007/s00262-004-0584-y
PUBMED: 15625606
PROVIDER: scopus
DOI/URL:

http://www.scopus.com/inward/record.url?eid=2-s2.0-17444428086&partnerID=40&md5=40f6020502d794fb2b92dee782ca814f
Notes: --- - "Cited By (since 1996): 53" - "Export Date: 24 October 2012" - "CODEN: CIIMD" - "Source: Scopus"
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MSK Authors
  1. Govindaswami Ragupathi
    144 Ragupathi
  2. Samuel J Danishefsky
    539 Danishefsky
  3. San S Yi
    14 Yi
  4. Philip O Livingston
    228 Livingston
  5. Ella Kagan
    9 Kagan
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