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Fully synthetic carbohydrate-based vaccines in biochemically relapsed prostate cancer: clinical trial results with alpha-N-acetylgalactosamine-O-serine/threonine conjugate vaccine.
- Source :
-
Journal of clinical oncology : official journal of the American Society of Clinical Oncology [J Clin Oncol] 2003 Dec 01; Vol. 21 (23), pp. 4292-8. - Publication Year :
- 2003
-
Abstract
- Purpose: We report the synthesis of a mucin-related O-linked glycopeptide, alpha-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.<br />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 microg of Tn(c) per vaccination. Ten patients received 100 microg 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.<br />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.<br />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.
- Subjects :
- Aged
Aged, 80 and over
Antigens, Tumor-Associated, Carbohydrate chemistry
Antigens, Tumor-Associated, Carbohydrate immunology
Biomarkers, Tumor blood
Cancer Vaccines chemical synthesis
Cancer Vaccines chemistry
Cancer Vaccines immunology
Carbohydrate Sequence
Complement System Proteins immunology
Cytotoxicity Tests, Immunologic
Hemocyanins chemistry
Hemocyanins metabolism
Humans
Immunoglobulin G blood
Immunoglobulin M blood
Male
Middle Aged
Molecular Sequence Data
Mucins immunology
Neoplasm Recurrence, Local immunology
Neoplasm Recurrence, Local prevention & control
Palmitic Acid chemistry
Palmitic Acid metabolism
Prostate-Specific Antigen blood
Prostatic Neoplasms immunology
Vaccination
Vaccines, Conjugate chemistry
Vaccines, Conjugate immunology
Antigens, Tumor-Associated, Carbohydrate therapeutic use
Cancer Vaccines therapeutic use
Neoplasm Recurrence, Local therapy
Prostatic Neoplasms therapy
Vaccines, Conjugate therapeutic use
Subjects
Details
- Language :
- English
- ISSN :
- 0732-183X
- Volume :
- 21
- Issue :
- 23
- Database :
- MEDLINE
- Journal :
- Journal of clinical oncology : official journal of the American Society of Clinical Oncology
- Publication Type :
- Academic Journal
- Accession number :
- 14645418
- Full Text :
- https://doi.org/10.1200/JCO.2003.04.112