Immunization of metastatic breast cancer patients with a fully synthetic globo H conjugate: A phase I trial Journal Article

   


Authors: Gilewski, T.; Ragupathi, G.; Bhuta, S.; Williams, L. J.; Musselli, C.; Zhang, X. F.; Bencsath, K. P.; Panageas, K. S.; Chin, J.; Hudis, C. A.; Norton, L.; Houghton, A. N.; Livingston, P. O.; Danishefsky, S. J.
Article Title: Immunization of metastatic breast cancer patients with a fully synthetic globo H conjugate: A phase I trial
Abstract: The carbohydrate antigen globo H commonly found on breast cancer cells is a potential target for vaccine therapy. The objectives of this trial were to determine the toxicity and immunogenicity of three synthetic globo H-keyhole limpet hemocyanin conjugates plus the immunologic adjuvant QS-21. Twenty-seven metastatic breast cancer patients received five vaccinations each. The vaccine was well tolerated, and no definite differences were observed among the three formulations. Serologic analyses demonstrated the generation of IgM antibody titers in most patients, with minimal IgG antibody stimulation. There was significant binding of IgM antibodies to MCF-7 tumor cells in 16 patients, whereas IgG antibody reactivity was observed in a few patients. There was evidence of complement-dependent cytotoxicity in several patients. Affinity column purification supported the specificity of IgM antibodies for globo H. On the basis of these data, globo H will constitute one component of a polyvalent vaccine for evaluation in high-risk breast cancer patients.
Keywords: adult; clinical article; controlled study; treatment outcome; bone neoplasms; middle aged; unclassified drug; human cell; clinical trial; drug tolerability; fatigue; liver neoplasms; lymphatic metastasis; metastasis; controlled clinical trial; breast cancer; randomized controlled trial; lung neoplasms; myalgia; breast neoplasms; enzyme linked immunosorbent assay; fever; pruritus; rigor; molecular sequence data; cancer vaccine; cancer vaccines; antibody response; cancer immunization; neoplasm metastasis; headache; phase 1 clinical trial; immunoglobulin g antibody; drug conjugation; carbohydrate sequence; carbohydrate antigen; antibody titer; drug formulation; complement dependent cytotoxicity; keyhole limpet hemocyanin; immunoglobulin m antibody; vaccines, conjugate; immunization; globo h antigen; qs 21; cancer antibody; humans; human; female; priority journal; article; mink cell focus-forming virus
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: 3270
End Page: 3275
Language: English
DOI: 10.1073/pnas.051626298
PUBMED: 11248068
PROVIDER: scopus
PMCID: PMC30643
DOI/URL:

http://www.scopus.com/inward/record.url?eid=2-s2.0-0035853030&partnerID=40&md5=53d822f0219aac730fb506bddcba15a4
Notes: Export Date: 21 May 2015 -- Source: Scopus
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MSK Authors
  1. Clifford Hudis
    905 Hudis
  2. Larry Norton
    758 Norton
  3. Teresa A Gilewski
    97 Gilewski
  4. Cristina Musselli
    16 Musselli
  5. Lawrence J Williams
    14 Williams
  6. Govindaswami Ragupathi
    144 Ragupathi
  7. Katherine S Panageas
    512 Panageas
  8. Samuel J Danishefsky
    539 Danishefsky
  9. Philip O Livingston
    228 Livingston
  10. Alan N Houghton
    364 Houghton
  11. Sonal M Bhuta
    3 Bhuta
  12. Jeannette Chin-Eng
    5 Chin-Eng
  13. Xufang Zhang
    6 Zhang
  14. Kalman P Bencsath
    1 Bencsath
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