Carbohydrate vaccines in cancer: Immunogenicity of a fully synthetic globo H hexasaccharide conjugate in man Journal Article
| Authors: | Slovin, S. F.; Ragupathi, G.; Adluri, S.; Ungers, G.; Terry, K.; Kim, S.; Spassova, M.; Bornmann, W. G.; Fazzari, M.; Dantis, L.; Olkiewicz, K.; Lloyd, K. O.; Livingston, P. O.; Danishefsky, S. J.; Scher, H. I. |
| Article Title: | Carbohydrate vaccines in cancer: Immunogenicity of a fully synthetic globo H hexasaccharide conjugate in man |
| Abstract: | The complex carbohydrate molecule globo H hexasaccharide has been synthesized, conjugated to keyhole limpet hemocyanin, and administered with the immunologic adjuvant QS-21 as a vaccine for patients with prostate cancer who have relapsed after primary therapies such as radiation or surgery. Globo H is one of several candidate antigens present on prostate cancer cells that can serve as targets for immune recognition and treatment strategies. The vaccine, given as five subcutaneous vaccinations over 26 weeks, has been shown to be safe and capable of inducing specific high-titer IgM antibodies against globo H. Its immunogenicity was confirmed in prostate cancer patients with a broad range of stages and tumor burdens. Observations of several patients who had evidence of disease relapse restricted to a rising biochemical marker, prostate-specific antigen (PSA), indicated that a treatment effect could occur within 3 months after completion of the vaccine therapy. This effect was manifested as a decline of the slope of the log of PSA concentration vs. time plot after treatment compared with values before treatment. Five patients continue to have stable PSA slope profiles in the absence of any radiographic evidence of disease for more than 2 years. The concept of using PSA slope profiles in assessing early treatment effects in biological therapies such as vaccines awaits further validation in phase II and III trials. The use of a variety of lesser known candidate glycoprotein and carbohydrate antigens in prostate cancer serves as a focus for the development of a multivalent vaccine of the treatment of relapsed prostate cancer in patients with minimal tumor burden. |
| Keywords: | clinical article; controlled study; aged; middle aged; unclassified drug; human cell; clinical trial; drug efficacy; patient selection; prostate specific antigen; controlled clinical trial; tumor markers, biological; time factors; prostate cancer; prostate-specific antigen; prostatic neoplasms; cancer inhibition; molecular sequence data; immunoglobulin g; cancer vaccine; cancer vaccines; immunogenicity; antibody response; vaccination; antibodies; vaccine production; carbohydrate sequence; antibody titer; keyhole limpet hemocyanin; immunoglobulin m; vaccines, conjugate; oligosaccharide; qs 21; cytotoxicity tests, immunologic; subcutaneous drug administration; complement system proteins; humans; human; male; priority journal; article; globo h hexasaccharide conjugate |
| Journal Title: | Proceedings of the National Academy of Sciences of the United States of America |
| Volume: | 96 |
| Issue: | 10 |
| ISSN: | 0027-8424 |
| Publisher: | National Academy of Sciences |
| Date Published: | 1999-05-01 |
| Start Page: | 5710 |
| End Page: | 5715 |
| Language: | English |
| DOI: | 10.1073/pnas.96.10.5710 |
| PUBMED: | 10318949 |
| PROVIDER: | scopus |
| PMCID: | PMC21925 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 16 August 2016 -- Source: Scopus |
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