Toward optimized carbohydrate-based anticancer vaccines: Epitope clustering, carrier structure, and adjuvant all influence antibody responses to Lewisy conjugates in mice Journal Article

   


Authors: Kudryashov, V.; Glunz, P. W.; Williams, L. J.; Hintermann, S.; Danishefsky, S. J.; Lloyd, K. O.
Article Title: Toward optimized carbohydrate-based anticancer vaccines: Epitope clustering, carrier structure, and adjuvant all influence antibody responses to Lewisy conjugates in mice
Abstract: The feasibility of using carbohydrate-based vaccines for the immunotherapy of cancer is being actively explored at the present time. Although a number of clinical trials have already been conducted with glycoconjugate vaccines, the optimal design and composition of the vaccines has yet to be determined. Among the candidate antigens being examined is Lewisy (Ley), a blood group-related antigen that is overexpressed on the majority of human carcinomas. Using Ley as a model for specificity, we have examined the role of epitope clustering, carrier structure, and adjuvant on the immunogenicity of Ley conjugates in mice. A glycolipopeptide containing a cluster of three contiguous Ley-serine epitopes and the Pam3Cys immunostimulating moiety was found to be superior to a similar construct containing only one Ley-serine epitope in eliciting antitumor cell antibodies. Because only IgM antibodies were produced by this vaccine, the effect on immunogenicity of coupling the glycopeptide to keyhole limpet hemocyanin was examined; although both IgM and IgG antibodies were formed, the antibodies reacted only with the immunizing structure. Reexamination of the clustered Ley-serine Pam3Cys conjugate with the adjuvant QS-21 resulted in the identification of both IgG and IgM antibodies reacting with tumor cells, thus demonstrating the feasibility of an entirely synthetic carbohydrate-based anticancer vaccine in an animal model.
Keywords: controlled study; nonhuman; mouse; animals; mice; cancer immunotherapy; animal experiment; drug structure; mice, inbred balb c; mice, inbred c57bl; animalia; molecular sequence data; cancer vaccine; cancer vaccines; immunogenicity; antibody response; epitope; immunostimulation; adjuvants, immunologic; epitopes, b-lymphocyte; antibodies, neoplasm; immunoglobulin g antibody; carbohydrate sequence; carbohydrates; glycopeptide; keyhole limpet hemocyanin; immunoglobulin m antibody; lewis blood-group system; vaccines, conjugate; cancer antibody; adjuvant; lipoproteins; blood group lewis system; priority journal; article
Journal Title: Proceedings of the National Academy of Sciences of the United States of America
Volume: 98
Issue: 6
ISSN: 0027-8424
Publisher: National Academy of Sciences  
Date Published: 2001-03-13
Start Page: 3264
End Page: 3269
Language: English
DOI: 10.1073/pnas.051623598
PUBMED: 11248067
PROVIDER: scopus
PMCID: PMC30642
DOI/URL:

http://www.scopus.com/inward/record.url?eid=2-s2.0-0035853029&partnerID=40&md5=5e34a0d66d1418d91ffb5afda309e31a
Notes: Export Date: 21 May 2015 -- Source: Scopus
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MSK Authors
  1. Valery Kudryashov
    15 Kudryashov
  2. Samuel Hintermann
    3 Hintermann
  3. Peter W Glunz
    11 Glunz
  4. Lawrence J Williams
    14 Williams
  5. Samuel J Danishefsky
    539 Danishefsky
  6. Kenneth O Lloyd
    163 Lloyd
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