期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 101, 期 33, 页码 11937-11942出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0401894101
关键词
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资金
- NCI NIH HHS [R37 CA028824, CA-28824, R01 CA028824] Funding Source: Medline
- NIAID NIH HHS [F32 AI051883, AI-51883, AI-16943] Funding Source: Medline
Vaccines derived from totally synthetic carbohydrate antigens have been shown to elicit an immune response in both preclinical and clinical settings. The vaccines have been proven safe when administered in human clinical trials and are also competent at inducing antibodies that react with aberrant cells expressing the corresponding carbohydrate antigen. The most well studied vaccines have hitherto focused on single carbohydrate antigens, notwithstanding the known heterogeneity of transformed cells. Advances in synthetic organic chemistry have enabled the preparation and subsequent investigation of vaccines that contain several different tumor-associated carbohydrate antigens in a single molecule. These unimolecular constructs could, in principle, serve as superior mimics of cell surface antigens and hence, as multifaceted cancer vaccines. We report here the synthesis of a pentameric vaccine targeting a specific cancer. The new vaccine contains prostate tumor-associated antigens, Tn, TF, STn, Lewis(y), and Globo-H. To reach our goal, antigen-containing amino acid monomers were assembled in a linear fashion to form a glycopeptide containing the five distinct carbohydrate antigen units. The attachment of a linker to the glycopeptide followed by an extraordinary global deprotection and subsequent conjugation to two different immunogenic carriers, keyhole limpet hemocyanin and N-alpha-palmitoyi-S-[2,3-bis(palmitoyl-oxy)-(2RS)-propyl]-L-cysteine,resulted in the vaccine constructs. The results described herein indicate that complex unimolecular multivalent vaccines can be efficiently produced in the laboratory. These fully synthetic vaccines have the potential to stimulate a multifaceted immune response against prostate cancer.
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