Immunization of ovarian cancer patients with a synthetic Lewis(y)- protein conjugate vaccine: A phase 1 trial Journal Article

  


Authors: Sabbatini, P. J.; Kudryashov, V.; Ragupathi, G.; Danishefsky, S. J.; Livingston, P. O.; Bornmann, W.; Spassova, M.; Zatorski, A.; Spriggs, D.; Aghajanian, C.; Soignet, S.; Peyton, M.; O'Flaherty, C.; Curtin, J.; Lloyd, K. O.
Article Title: Immunization of ovarian cancer patients with a synthetic Lewis(y)- protein conjugate vaccine: A phase 1 trial
Abstract: As the initial step in developing carbohydrate-based vaccines for the treatment of ovarian cancer patients in an adjuvant setting, 25 patients were immunized with a Lewis(y) pentasaccharide (Le(y))-keyhole limpet hemocyanin (KLH)conjugate vaccine together with the immunological adjuvant QS-21. Four different doses of the vaccine, containing 3, 10, 30, and 60 μg of carbohydrate were administered s.c. at 0, 1, 2, 3, 7, and 19 weeks to groups of 6 patients. Sera taken from the patients at regular intervals were assayed by ELISA for reactivity with naturally occurring forms of Le(y) (Le(y)- ceramide and Le(y) mucin) and by flow cytometry and a complement-dependent cytoxicity assay for reactivity with Le(y)-expressing tumor cells. The majority of the patients (16/24) produced anti-Le(y) antibodies as assessed by ELISA, and a proportion of these had strong anti-tumor cell reactivity as assessed by flow cytometry and complement-dependent cytotoxicity. One serum, analyzed in detail, was shown to react with glycolipids but not with glycoproteins or mucins expressed by ovarian cancer cell line OVCAR-3. The vaccine was well tolerated and no gastrointestinal, hematologic, renal, or hepatic toxicity related to the vaccine was observed. On the basis of this study, Le(y)-KLH should be a suitable component for a polyvalent vaccine under consideration for the therapy of epithelial cancers. (C) 2000 Wiley- Liss, Inc.
Keywords: adult; clinical article; treatment outcome; aged; middle aged; clinical trial; cancer patient; flow cytometry; antigen expression; ovarian neoplasms; ovary cancer; tumor cells, cultured; enzyme linked immunosorbent assay; time factors; immune response; molecular sequence data; cancer vaccine; cancer vaccines; antibody response; epithelium cell; target cell; phase 1 clinical trial; enzyme-linked immunosorbent assay; adjuvants, immunologic; carcinoma, endometrioid; glycoprotein; carbohydrate sequence; complement dependent cytotoxicity; keyhole limpet hemocyanin; hemocyanin; lewis blood-group system; saponins; vaccines, conjugate; immunization; cystadenocarcinoma, papillary; chromatography, thin layer; humans; human; female; priority journal; article
Journal Title: International Journal of Cancer
Volume: 87
Issue: 1
ISSN: 0020-7136
Publisher: John Wiley & Sons  
Date Published: 2000-07-01
Start Page: 79
End Page: 85
Language: English
PUBMED: 10861456
PROVIDER: scopus
DOI: 10.1002/1097-0215(20000701)87:1<79::AID-IJC12>3.0.CO;2-L
DOI/URL:

http://www.scopus.com/inward/record.url?eid=2-s2.0-0004825568&partnerID=40&md5=ef4dc2e01a158479595e03b60ce4c149
Notes: Export Date: 18 November 2015 -- Source: Scopus
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MSK Authors
  1. William Bornmann
    112 Bornmann
  2. Andrzej Zatorski
    23 Zatorski
  3. Valery Kudryashov
    15 Kudryashov
  4. John P Curtin
    112 Curtin
  5. Steven L Soignet
    53 Soignet
  6. Paul J Sabbatini
    262 Sabbatini
  7. Govindaswami Ragupathi
    144 Ragupathi
  8. Samuel J Danishefsky
    539 Danishefsky
  9. Carol A Aghajanian
    607 Aghajanian
  10. David R Spriggs
    325 Spriggs
  11. Maria K Spassova
    25 Spassova
  12. Philip O Livingston
    228 Livingston
  13. Catherine A O'Flaherty
    12 O'Flaherty
  14. Kenneth O Lloyd
    163 Lloyd
  15. Madeline Peyton
    2 Peyton
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