A strategy for generating cancer-specific monoclonal antibodies to aberrant O-glycoproteins: identification of a novel dysadherin-Tn antibody

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt

Standard

A strategy for generating cancer-specific monoclonal antibodies to aberrant O-glycoproteins : identification of a novel dysadherin-Tn antibody. / Steentoft, Catharina; Fuhrmann, Max; Battisti, Federico; Van Coillie, Julie; Madsen, Thomas D; Campos, Diana; Halim, Adnan; Vakhrushev, Sergey Y; Joshi, Hiren; Schreiber, Hans; Mandel, Ulla; Narimatsu, Yoshiki.

I: Glycobiology, Bind 29, Nr. 4, 2019, s. 307-319.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt

Harvard

Steentoft, C, Fuhrmann, M, Battisti, F, Van Coillie, J, Madsen, TD, Campos, D, Halim, A, Vakhrushev, SY, Joshi, H, Schreiber, H, Mandel, U & Narimatsu, Y 2019, 'A strategy for generating cancer-specific monoclonal antibodies to aberrant O-glycoproteins: identification of a novel dysadherin-Tn antibody', Glycobiology, bind 29, nr. 4, s. 307-319. https://doi.org/10.1093/glycob/cwz004

APA

Steentoft, C., Fuhrmann, M., Battisti, F., Van Coillie, J., Madsen, T. D., Campos, D., Halim, A., Vakhrushev, S. Y., Joshi, H., Schreiber, H., Mandel, U., & Narimatsu, Y. (2019). A strategy for generating cancer-specific monoclonal antibodies to aberrant O-glycoproteins: identification of a novel dysadherin-Tn antibody. Glycobiology, 29(4), 307-319. https://doi.org/10.1093/glycob/cwz004

Vancouver

Steentoft C, Fuhrmann M, Battisti F, Van Coillie J, Madsen TD, Campos D o.a. A strategy for generating cancer-specific monoclonal antibodies to aberrant O-glycoproteins: identification of a novel dysadherin-Tn antibody. Glycobiology. 2019;29(4):307-319. https://doi.org/10.1093/glycob/cwz004

Author

Steentoft, Catharina ; Fuhrmann, Max ; Battisti, Federico ; Van Coillie, Julie ; Madsen, Thomas D ; Campos, Diana ; Halim, Adnan ; Vakhrushev, Sergey Y ; Joshi, Hiren ; Schreiber, Hans ; Mandel, Ulla ; Narimatsu, Yoshiki. / A strategy for generating cancer-specific monoclonal antibodies to aberrant O-glycoproteins : identification of a novel dysadherin-Tn antibody. I: Glycobiology. 2019 ; Bind 29, Nr. 4. s. 307-319.

Bibtex

@article{f22c0c8720a94f6a93389d6c5e3af04e,
title = "A strategy for generating cancer-specific monoclonal antibodies to aberrant O-glycoproteins: identification of a novel dysadherin-Tn antibody",
abstract = "Successful application of potent antibody-based T-cell engaging immunotherapeutic strategies is currently limited mainly to hematological cancers. One major reason is the lack of well-characterized antigens on solid tumors with sufficient cancer specific expression. Aberrantly O-glycosylated proteins contain promising cancer-specific O-glycopeptide epitopes suitable for immunotherapeutic applications, but currently only few examples of such antibody epitopes have been identified. We previously showed that chimeric antigen receptor T-cells directed towards aberrantly O-glycosylated MUC1 can control malignant growth in a mouse model. Here, we present a discovery platform for the generation of cancer-specific monoclonal antibodies targeting aberrant O-glycoproteins. The strategy is based on cancer cell lines engineered to homogeneously express the truncated Tn O-glycoform, the so-called SimpleCells. We used SimpleCells of different cancer origin to elicit monoclonal antibodies with selectivity for aberrant O-glycoproteins. For validation we selected and characterized one monoclonal antibody (6C5) directed to a Tn-glycopeptide in dysadherin (FXYD5), known to be upregulated in cancer and promote metastasis. While dysadherin is widely expressed also in normal cells, we demonstrated that the 6C5 epitope is specifically expressed in cancer.",
author = "Catharina Steentoft and Max Fuhrmann and Federico Battisti and {Van Coillie}, Julie and Madsen, {Thomas D} and Diana Campos and Adnan Halim and Vakhrushev, {Sergey Y} and Hiren Joshi and Hans Schreiber and Ulla Mandel and Yoshiki Narimatsu",
year = "2019",
doi = "10.1093/glycob/cwz004",
language = "English",
volume = "29",
pages = "307--319",
journal = "Glycobiology",
issn = "0959-6658",
publisher = "Oxford University Press",
number = "4",

}

RIS

TY - JOUR

T1 - A strategy for generating cancer-specific monoclonal antibodies to aberrant O-glycoproteins

T2 - identification of a novel dysadherin-Tn antibody

AU - Steentoft, Catharina

AU - Fuhrmann, Max

AU - Battisti, Federico

AU - Van Coillie, Julie

AU - Madsen, Thomas D

AU - Campos, Diana

AU - Halim, Adnan

AU - Vakhrushev, Sergey Y

AU - Joshi, Hiren

AU - Schreiber, Hans

AU - Mandel, Ulla

AU - Narimatsu, Yoshiki

PY - 2019

Y1 - 2019

N2 - Successful application of potent antibody-based T-cell engaging immunotherapeutic strategies is currently limited mainly to hematological cancers. One major reason is the lack of well-characterized antigens on solid tumors with sufficient cancer specific expression. Aberrantly O-glycosylated proteins contain promising cancer-specific O-glycopeptide epitopes suitable for immunotherapeutic applications, but currently only few examples of such antibody epitopes have been identified. We previously showed that chimeric antigen receptor T-cells directed towards aberrantly O-glycosylated MUC1 can control malignant growth in a mouse model. Here, we present a discovery platform for the generation of cancer-specific monoclonal antibodies targeting aberrant O-glycoproteins. The strategy is based on cancer cell lines engineered to homogeneously express the truncated Tn O-glycoform, the so-called SimpleCells. We used SimpleCells of different cancer origin to elicit monoclonal antibodies with selectivity for aberrant O-glycoproteins. For validation we selected and characterized one monoclonal antibody (6C5) directed to a Tn-glycopeptide in dysadherin (FXYD5), known to be upregulated in cancer and promote metastasis. While dysadherin is widely expressed also in normal cells, we demonstrated that the 6C5 epitope is specifically expressed in cancer.

AB - Successful application of potent antibody-based T-cell engaging immunotherapeutic strategies is currently limited mainly to hematological cancers. One major reason is the lack of well-characterized antigens on solid tumors with sufficient cancer specific expression. Aberrantly O-glycosylated proteins contain promising cancer-specific O-glycopeptide epitopes suitable for immunotherapeutic applications, but currently only few examples of such antibody epitopes have been identified. We previously showed that chimeric antigen receptor T-cells directed towards aberrantly O-glycosylated MUC1 can control malignant growth in a mouse model. Here, we present a discovery platform for the generation of cancer-specific monoclonal antibodies targeting aberrant O-glycoproteins. The strategy is based on cancer cell lines engineered to homogeneously express the truncated Tn O-glycoform, the so-called SimpleCells. We used SimpleCells of different cancer origin to elicit monoclonal antibodies with selectivity for aberrant O-glycoproteins. For validation we selected and characterized one monoclonal antibody (6C5) directed to a Tn-glycopeptide in dysadherin (FXYD5), known to be upregulated in cancer and promote metastasis. While dysadherin is widely expressed also in normal cells, we demonstrated that the 6C5 epitope is specifically expressed in cancer.

U2 - 10.1093/glycob/cwz004

DO - 10.1093/glycob/cwz004

M3 - Journal article

C2 - 30726901

VL - 29

SP - 307

EP - 319

JO - Glycobiology

JF - Glycobiology

SN - 0959-6658

IS - 4

ER -

ID: 214298575