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

T. Gilewski, G. Ragupathi, S. Bhuta, L. J. Williams, C. Musselli, X. F. Zhang, K. P. Bencsath, K. S. Panageas, J. Chin, C. A. Hudis, L. Norton, A. N. Houghton, P. O. Livingston, S. J. Danishefsky

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174 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)3270-3275
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume98
Issue number6
DOIs
StatePublished - Mar 13 2001
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • General

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