From synthesis to biologics: Preclinical data on a chemistry derived anticancer vaccine Journal Article

   


Authors: Zhu, J.; Wan, Q.; Lee, D.; Yang, G.; Spassova, M. K.; Ouerfelli, O.; Ragupathi, G.; Damani, P.; Livingston, P. O.; Danishefsky, S. J.
Article Title: From synthesis to biologics: Preclinical data on a chemistry derived anticancer vaccine
Abstract: A fully synthetic anticancer vaccine 2 has been prepared via bioconjugation of unimolecular pentavalent construct 1 - containing five prostate and breast cancer associated carbohydrate antigens, Globo-H, GM2, STn, TF and Tn - to maleimide-modified carrier protein KLH. An improved conjugation protocol has been developed, which allowed us to obtain a higher epitope ratio of the unimolecular pentavalent glycopeptide antigen to the carrier protein (505/1 versus 228/1 for the previous version). KLH conjugate 2 has been subsequently submitted to preclinical immunogenic evaluation in mice in the presence of QS-21 as an adjuvant. Through standard ELISA assay, this vaccine candidate showed high promise in inducing IgG and IgM antibodies against each of the five individual carbohydrate antigens. In addition, FACS analysis indicated that these antibodies were able to react with MCF-7 breast cancer cell lines expressing these five carbohydrate antigens. © 2009 American Chemical Society.
Keywords: controlled study; carrier protein; unclassified drug; human cell; nonhuman; adjuvant therapy; antigen expression; mouse; animals; mice; breast cancer; animal experiment; cell line, tumor; drug synthesis; immunoreactivity; breast neoplasms; tumor antigen; enzyme linked immunosorbent assay; mice, inbred c57bl; prostate cancer; prostatic neoplasms; antigens; cancer vaccine; cell culture; cancer vaccines; immunogenicity; carrier proteins; vaccines, synthetic; antibodies; cell strain mcf 7; fluorescence activated cell sorting; immunoglobulin g antibody; drug conjugation; antigens, tumor-associated, carbohydrate; carbohydrates; carbohydrate antigen; glycopeptide; stn antigen; tn antigen; antibody formation; antibody production; vaccines; immunoglobulin m antibody; hemocyanin; maleimides; bio-conjugation; elisa assay; maleimide; mcf-7 breast cancer cells; unimolecular; globo h antigen; gm2 antigen; klh carrier protein; qs 21; tf antigen; upc klh vaccine; binding sites, antibody
Journal Title: Journal of the American Chemical Society
Volume: 131
Issue: 26
ISSN: 0002-7863
Publisher: American Chemical Society  
Date Published: 2009-07-08
Start Page: 9298
End Page: 9303
Language: English
DOI: 10.1021/ja901415s
PUBMED: 19518111
PROVIDER: scopus
PMCID: PMC2716484
DOI/URL:

http://www.scopus.com/inward/record.url?eid=2-s2.0-67649980009&partnerID=40&md5=fe43e9466a86cc49265f342591fc85c4
Notes: --- - "Cited By (since 1996): 5" - "Export Date: 30 November 2010" - "CODEN: JACSA" - "Source: Scopus"
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MSK Authors
  1. Qian Wan
    23 Wan
  2. Govindaswami Ragupathi
    144 Ragupathi
  3. Jianglong Zhu
    14 Zhu
  4. Samuel J Danishefsky
    539 Danishefsky
  5. Ouathek Ouerfelli
    100 Ouerfelli
  6. Maria K Spassova
    25 Spassova
  7. Guangbin Yang
    27 Yang
  8. Dongjoo Lee
    6 Lee
  9. Philip O Livingston
    228 Livingston
  10. Payal Damani
    9 Damani
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