Fully synthetic carbohydrate-based vaccines in biochemically relapsed prostate cancer: Clinical trial results with α-N-acetylgalactosamine-O- serine/threonine conjugate vaccine Journal Article

Authors: Slovin, S. F.; Ragupathi, G.; Musselli, C.; Olkiewicz, K.; Verbel, D.; Kuduk, S. D.; Schwarz, J. B.; Sames, D.; Danishefsky, S.; Livingston, P. O.; Scher, H. I.
Article Title: Fully synthetic carbohydrate-based vaccines in biochemically relapsed prostate cancer: Clinical trial results with α-N-acetylgalactosamine-O- serine/threonine conjugate vaccine
Abstract: Purpose: We report the synthesis of a mucin-related O-linked glycopeptide, α-N-acetylgalactosamine-O-serine/threonine (Tn), which is highly simplistic in its structure and can induce a relevant humoral response when given in a trimer or clustered (c) formation. We tested for an antitumor effect, in the form of a change in the posttreatment versus pretreatment prostate-specific antigen (PSA) slopes, that might serve as a surrogate for effectiveness of vaccines in delaying the time to radiographic progression. Methods: We compared the antibody response to immunization with two conjugates, Tn(c)-keyhole limpet hemocyanin (KLH) and Tn(c)-palmitic acid (PAM) with the saponin immunologic adjuvant QS21, in a phase I clinical trial in patients with biochemically relapsed prostate cancer. Patients received Tn(c)-KLH vaccine containing either 3, 7, or 15 μg of Tn(c) per vaccination. Ten patients received 100 μg of Tn(c)-PAM. QS21 was included in all vaccines. Five vaccinations were administered subcutaneously during 26 weeks with an additional booster vaccine at week 50. Results: Tn(c), when given with the carrier molecule KLH and QS21, stimulated the production of high-titer immunoglobulin M (IgM) and IgG antibodies. Inferior antibody responses were seen with T(c)-PAM. There was no evidence of enhanced immunogenicity with increasing doses of vaccine. An antitumor effect in the form of a decline in posttreatment versus pretreatment PSA slopes was also observed. Conclusion: A safe synthetic conjugate vaccine in a trimer formation was developed that can break immunologic tolerance by inducing specific humoral responses. It seemed to affect the biochemical progression of the disease as determined by a change in PSA log slope. © 2003 by American Society of Clinical Oncology.
Keywords: controlled study; aged; aged, 80 and over; middle aged; unclassified drug; clinical trial; cancer growth; drug efficacy; comparative study; molecular genetics; prostate specific antigen; metabolism; controlled clinical trial; neoplasm recurrence, local; tumor markers, biological; drug structure; drug synthesis; tumor antigen; tumor marker; prostate cancer; prostate-specific antigen; prostatic neoplasms; blood; immunology; chemistry; molecular sequence data; immunoglobulin g; cancer vaccine; cancer vaccines; tumor recurrence; prostate tumor; antibody response; vaccination; cancer relapse; phase 1 clinical trial; structure analysis; humoral immunity; synthesis; vaccine; carbohydrate analysis; antigens, tumor-associated, carbohydrate; carbohydrate sequence; tn antigen; carbohydrate; keyhole limpet hemocyanin; complement; hemocyanin; immunoglobulin m; vaccines, conjugate; immunization; mucin; mucins; qs 21; cytotoxicity tests, immunologic; cytotoxicity test; palmitic acid; complement system proteins; humans; human; male; priority journal; article; alpha n acetylgalactosamine o serine threonine keyhole limpet hemocyanin; alpha n acetylgalactosamine o serine threonine palmitic acid; keyhole-limpet hemocyanin
Journal Title: Journal of Clinical Oncology
Volume: 21
Issue: 23
ISSN: 0732-183X
Publisher: American Society of Clinical Oncology  
Date Published: 2003-12-01
Start Page: 4292
End Page: 4298
Language: English
DOI: 10.1200/jco.2003.04.112
PUBMED: 14645418
PROVIDER: scopus
Notes: Export Date: 12 September 2014 -- Source: Scopus
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MSK Authors
  1. Susan Slovin
    184 Slovin
  2. Dalibor Sames
    9 Sames
  3. David A Verbel
    20 Verbel
  4. Scott D Kuduk
    21 Kuduk
  5. Govindaswami Ragupathi
    133 Ragupathi
  6. Howard Scher
    816 Scher