Reactivity of natural and induced human antibodies to MUC1 mucin with MUC1 peptides and N-acetylgalactosamine (GalNAc) peptides

• Type: Article in International Scientific Journal
• Date: 2000

Authors

von Mensdorff Pouilly, S (Author) Other; Petrakou, E (Author) Other; Kenemans, P (Author) Other; van Uffelen, K (Author) Other; Verstraeten, AA (Author) Other; Snijdewint, FGM (Author) Other; van Kamp, GJ (Author) Other; Schol, DJ (Author) Other; Celso Reis (Author) Other; Price, MR (Author) Other; Livingston, PO (Author) Other; Hilgers, J (Author) Other

Journal

Title: International Journal of Cancer

Vol. 86

Pages: 702-712

ISSN: 0020-7136

Publisher: Wiley-Blackwell

Indexing

ISI Web of Knowledge - 114 Citations

Scopus - 114 Citations

Other information

Authenticus ID: P-008-NPF

DOI: 10.1002/(sici)1097-0215(20000601)86:5<702::aid-ijc16>3.0.co;2-1

Abstract (EN): Antibodies (Abs) to MUCI occur naturally in both healthy subjects and cancer patients and can be induced by MUCI peptide vaccination. We compared the specificity of natural and induced MUCI Abs with the objective of defining an effective MUCI vaccine for active immunotherapy of adenocarcinoma patients. Serum samples, selected out of a screened population of 492 subjects for their high levels of IgG and/or IgM MUCI Abs, were obtained from 55 control subjects and from 26 breast cancer patients before primary treatment, as well as from 19 breast cancer patients immunized with MUCI peptides coupled to keyhole limpet hemocyanin (KLH) and mixed with QS-21, The samples were tested with enzyme-linked immunoassays for reactivity with (I) overlapping hepta- and 20-mer peptides spanning the MUCI tandem repeat sequence; (2) two modified 60-mer peptides with substitutions in the PDTR (PDTA) or in the STAPPA (STAAAA) sequence of each tandem repeat; and (3) four 60-mer glycopeptides with each I, 2, 3 and 5 mol N-acetylgalactosamine (GalNAc) per repeat. More than one minimal epitopic sequence could be defined, indicating that Abs directed to more than one region of the MUCI peptide core can coexist in one and the same subject. The most frequent minimal epitopic sequence of natural MUCI IgG and IgM Abs was RPAPGS, followed by PPAHGVT and PDTRP, MUCI peptide vaccination induced high titers of IgM and IgG Abs predominantly directed, respectively, to the PDTRPAP and the STAPPAHGV sequences of the tandem repeat. Natural MUCI Abs from breast cancer patients reacted more strongly with the N-acetylgalactosamine (GalNAc) peptides than with the naked 60-mer peptide, while reactivity with the GalNAc-peptides was significantly reduced (2-tailed p < 0.0001) in the MUCI IgG and IgM Abs induced by MUCI peptide vaccination. Whereas in cancer patients glycans appear to participate in epitope conformation, the epitope(s) recognized by MUCI Abs induced by peptide vaccination are already masked by minimal glycosylation, Therefore, our results indicate that a MUCI glycopeptide would be a better vaccine than a naked peptide. (C) 2000 Wiley-Liss, Inc.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 11