Chemoenzymatically synthesized multimeric Tn/STn MUC1 glycopeptides elicit cancer-specific anti-MUC1 antibody responses and override tolerance.

Anne Louise Sørensen; Celso A Reis; Mads A Tarp; Ulla Mandel; Kavitha Ramachandran; Vasanthi Sankaranarayanan; Tilo Schwientek; Ros Graham; Joyce Taylor-Papadimitriou; Michael A Hollingsworth; Joy Burchell; Henrik Clausen

doi:10.1093/glycob/cwj044

Chemoenzymatically synthesized multimeric Tn/STn MUC1 glycopeptides elicit cancer-specific anti-MUC1 antibody responses and override tolerance.

Anne Louise Sørensen, Celso A Reis, Mads A Tarp, Ulla Mandel, Kavitha Ramachandran, Vasanthi Sankaranarayanan, Tilo Schwientek, Ros Graham, Joyce Taylor-Papadimitriou, Michael A Hollingsworth, Joy Burchell, Henrik Clausen

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

226 Citationer (Scopus)

Abstract

Udgivelsesdato: 2006-Feb

Originalsprog	Engelsk
Tidsskrift	Glycobiology
Vol/bind	16
Udgave nummer	2
Sider (fra-til)	96-107
Antal sider	11
ISSN	0959-6658
DOI	https://doi.org/10.1093/glycob/cwj044
Status	Udgivet - 2005

Bibliografisk note

Keywords: Amino Acid Sequence; Animals; Antigens, Tumor-Associated, Carbohydrate; CA-15-3 Antigen; Cancer Vaccines; Cell Line; Glycopeptides; Humans; Immune Tolerance; Mice; Mice, Inbred BALB C; Mice, Transgenic; Molecular Sequence Data; Substrate Specificity

Adgang til dokumentet

10.1093/glycob/cwj044

Citationsformater

Sørensen, A. L., Reis, C. A., Tarp, M. A., Mandel, U., Ramachandran, K., Sankaranarayanan, V., Schwientek, T., Graham, R., Taylor-Papadimitriou, J., Hollingsworth, M. A., Burchell, J., & Clausen, H. (2005). Chemoenzymatically synthesized multimeric Tn/STn MUC1 glycopeptides elicit cancer-specific anti-MUC1 antibody responses and override tolerance. Glycobiology, 16(2), 96-107. https://doi.org/10.1093/glycob/cwj044

Sørensen, AL, Reis, CA, Tarp, MA, Mandel, U, Ramachandran, K, Sankaranarayanan, V, Schwientek, T, Graham, R, Taylor-Papadimitriou, J, Hollingsworth, MA, Burchell, J & Clausen, H 2005, 'Chemoenzymatically synthesized multimeric Tn/STn MUC1 glycopeptides elicit cancer-specific anti-MUC1 antibody responses and override tolerance.', Glycobiology, bind 16, nr. 2, s. 96-107. https://doi.org/10.1093/glycob/cwj044

@article{bceb42708bbc11dd9c20000ea68e967b,

title = "Chemoenzymatically synthesized multimeric Tn/STn MUC1 glycopeptides elicit cancer-specific anti-MUC1 antibody responses and override tolerance.",

abstract = "The MUC1 mucin represents a prime target antigen for cancer immunotherapy because it is abundantly expressed and aberrantly glycosylated in carcinomas. Attempts to generate strong humoral immunity to MUC1 by immunization with peptides have generally failed partly because of tolerance. In this study, we have developed chemoenzymatic synthesis of extended MUC1 TR glycopeptides with cancer-associated O-glycosylation using a panel of recombinant human glycosyltransferases. MUC1 glycopeptides with different densities of Tn and STn glycoforms conjugated to KLH were used as immunogens to evaluate an optimal vaccine design. Glycopeptides with complete O-glycan occupancy (five sites per repeat) elicited the strongest antibody response reacting with MUC1 expressed in breast cancer cell lines in both Balb/c and MUC1.Tg mice. The elicited humoral immune response showed remarkable specificity for cancer cells suggesting that the glycopeptide design holds promise as a cancer vaccine. The elicited immune responses were directed to combined glycopeptide epitopes, and both peptide sequence and carbohydrate structures were important for the antigen. A MAb (5E5) with similar specificity as the elicited immune response was generated and shown to have the same remarkable cancer specificity. This antibody may hold promise in diagnostic and immunopreventive measures.",

author = "S{\o}rensen, {Anne Louise} and Reis, {Celso A} and Tarp, {Mads A} and Ulla Mandel and Kavitha Ramachandran and Vasanthi Sankaranarayanan and Tilo Schwientek and Ros Graham and Joyce Taylor-Papadimitriou and Hollingsworth, {Michael A} and Joy Burchell and Henrik Clausen",

note = "Keywords: Amino Acid Sequence; Animals; Antigens, Tumor-Associated, Carbohydrate; CA-15-3 Antigen; Cancer Vaccines; Cell Line; Glycopeptides; Humans; Immune Tolerance; Mice; Mice, Inbred BALB C; Mice, Transgenic; Molecular Sequence Data; Substrate Specificity",

year = "2005",

doi = "10.1093/glycob/cwj044",

language = "English",

volume = "16",

pages = "96--107",

journal = "Glycobiology",

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TY - JOUR

T1 - Chemoenzymatically synthesized multimeric Tn/STn MUC1 glycopeptides elicit cancer-specific anti-MUC1 antibody responses and override tolerance.

AU - Sørensen, Anne Louise

AU - Reis, Celso A

AU - Tarp, Mads A

AU - Mandel, Ulla

AU - Ramachandran, Kavitha

AU - Sankaranarayanan, Vasanthi

AU - Schwientek, Tilo

AU - Graham, Ros

AU - Taylor-Papadimitriou, Joyce

AU - Hollingsworth, Michael A

AU - Burchell, Joy

AU - Clausen, Henrik

N1 - Keywords: Amino Acid Sequence; Animals; Antigens, Tumor-Associated, Carbohydrate; CA-15-3 Antigen; Cancer Vaccines; Cell Line; Glycopeptides; Humans; Immune Tolerance; Mice; Mice, Inbred BALB C; Mice, Transgenic; Molecular Sequence Data; Substrate Specificity

PY - 2005

Y1 - 2005

N2 - The MUC1 mucin represents a prime target antigen for cancer immunotherapy because it is abundantly expressed and aberrantly glycosylated in carcinomas. Attempts to generate strong humoral immunity to MUC1 by immunization with peptides have generally failed partly because of tolerance. In this study, we have developed chemoenzymatic synthesis of extended MUC1 TR glycopeptides with cancer-associated O-glycosylation using a panel of recombinant human glycosyltransferases. MUC1 glycopeptides with different densities of Tn and STn glycoforms conjugated to KLH were used as immunogens to evaluate an optimal vaccine design. Glycopeptides with complete O-glycan occupancy (five sites per repeat) elicited the strongest antibody response reacting with MUC1 expressed in breast cancer cell lines in both Balb/c and MUC1.Tg mice. The elicited humoral immune response showed remarkable specificity for cancer cells suggesting that the glycopeptide design holds promise as a cancer vaccine. The elicited immune responses were directed to combined glycopeptide epitopes, and both peptide sequence and carbohydrate structures were important for the antigen. A MAb (5E5) with similar specificity as the elicited immune response was generated and shown to have the same remarkable cancer specificity. This antibody may hold promise in diagnostic and immunopreventive measures.

AB - The MUC1 mucin represents a prime target antigen for cancer immunotherapy because it is abundantly expressed and aberrantly glycosylated in carcinomas. Attempts to generate strong humoral immunity to MUC1 by immunization with peptides have generally failed partly because of tolerance. In this study, we have developed chemoenzymatic synthesis of extended MUC1 TR glycopeptides with cancer-associated O-glycosylation using a panel of recombinant human glycosyltransferases. MUC1 glycopeptides with different densities of Tn and STn glycoforms conjugated to KLH were used as immunogens to evaluate an optimal vaccine design. Glycopeptides with complete O-glycan occupancy (five sites per repeat) elicited the strongest antibody response reacting with MUC1 expressed in breast cancer cell lines in both Balb/c and MUC1.Tg mice. The elicited humoral immune response showed remarkable specificity for cancer cells suggesting that the glycopeptide design holds promise as a cancer vaccine. The elicited immune responses were directed to combined glycopeptide epitopes, and both peptide sequence and carbohydrate structures were important for the antigen. A MAb (5E5) with similar specificity as the elicited immune response was generated and shown to have the same remarkable cancer specificity. This antibody may hold promise in diagnostic and immunopreventive measures.

U2 - 10.1093/glycob/cwj044

DO - 10.1093/glycob/cwj044

M3 - Journal article

C2 - 16207894

SN - 0959-6658

VL - 16

SP - 96

EP - 107

JO - Glycobiology

JF - Glycobiology

IS - 2

ER -