Synthetic and immunological studies on clustered modes of mucin-related Tn and TF O-linked antigens: The preparation of a glycopeptide-based vaccine for clinical trials against prostate cancer Journal Article

  

Authors:	Kuduk, S. D.; Schwarz, J. B.; Chen, X. T.; Glunz, P. W.; Sames, D.; Ragupathi, G.; Livingston, P. O.; Danishefsky, S. J.
Article Title:	Synthetic and immunological studies on clustered modes of mucin-related Tn and TF O-linked antigens: The preparation of a glycopeptide-based vaccine for clinical trials against prostate cancer
Abstract:	The syntheses of two tumor-associated carbohydrate antigens, Tn and TF, have been achieved using glycal assembly and cassette methodologies. These synthetic antigens were subsequently clustered (c) and immunoconjugated to a carrier protein (KLH or BSA) or a synthetic lipopeptide (pam) for immunological study. Three Tn conjugates were used to vaccinate groups of mice, and all preparations proved to be immunogenic. The Tn(c) covalently linked to KLH (27-KLH) plus the adjuvant QS-21 was the optimal vaccine, inducing high median IgM and IgG titers against Tn(c) by ELISA. These antibodies were strongly reactive with the Tn(c) positive human colon cancer cell line LS-C but not the Tn(c) negative colon cancer cell line LS-B by FACS. The antibodies' reactivities with natural antigens were inhibited with synthetic Tn(c) but not with structurally unrelated compounds. On the basis of these results, vaccines containing 27-KLH and 30-pam plus QS-21 are being tested in patients with prostate cancer.
Keywords:	carrier protein; protein assembly; enzyme linked immunosorbent assay; prostate cancer; amino acid sequence; cancer vaccine; immunogenicity; synthesis; carbohydrate antigen; glycopeptide; antibody titer; antibody conjugate; covalent bond; antigen antibody reaction; lipopeptide; article
Journal Title:	Journal of the American Chemical Society
Volume:	120
Issue:	48
ISSN:	0002-7863
Publisher:	American Chemical Society
Date Published:	1998-12-09
Start Page:	12474
End Page:	12485
Language:	English
DOI:	10.1021/ja9825128
PROVIDER:	scopus
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-0032501470&doi=10.1021%2fja9825128&partnerID=40&md5=e0eec490b6b19fe3ebfe83e18398438e
Notes:	Article -- Export Date: 12 December 2016 -- Source: Scopus

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