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MUC1 glycopeptide vaccine modified with a GalNAc glycocluster targets the macrophage galactose c-type lectin on dendritic cells to elicit an improved humoral response

Gabba, Adele (författare)
School of Biological and Chemical Sciences, University of Galway, University Rd., Galway, Ireland; Department of Chemistry, Johannes Gutenberg University Mainz, Duesbergweg 10−14, Mainz, Germany
Attariya, Riem (författare)
Institute of Immunology, University Medical Center Mainz, Langenbeckstr.1, Mainz, Germany
Behren, Sandra (författare)
Umeå universitet,Kemiska institutionen
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Pett, Christian (författare)
Umeå universitet,Kemiska institutionen
van der Horst, Joost C. (författare)
Department of Molecular Cell Biology and Immunology, Amsterdam UMC Location Vrije Universiteit Amsterdam, De Boelelaan 1117, Amsterdam, Netherlands; Amsterdam Institute for Infection and Immunity, Cancer Immunology, Amsterdam, Netherlands
Yurugi, Hajime (författare)
Institute of Immunology, University Medical Center Mainz, Langenbeckstr.1, Mainz, Germany
Yu, Jin (författare)
Glycosciences Laboratory, Imperial College London, London, United Kingdom
Urschbach, Moritz (författare)
Department of Chemistry, Johannes Gutenberg University Mainz, Duesbergweg 10−14, Mainz, Germany
Sabin, Juan (författare)
AFFINImeter Scientific & Development Team, Software 4 Science Developments, A Coruña, Santiago de Compostela, Spain; Departamento de Física Aplicada, Facultad de Física, Universidad de Santiago de Compostela, Santiago de Compostela, Spain
Birrane, Gabriel (författare)
Division of Experimental Medicine, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, MA, Boston, United States
Schmitt, Edgar (författare)
Institute of Immunology, University Medical Center Mainz, Langenbeckstr.1, Mainz, Germany
van Vliet, Sandra J. (författare)
Department of Molecular Cell Biology and Immunology, Amsterdam UMC Location Vrije Universiteit Amsterdam, De Boelelaan 1117, Amsterdam, Netherlands; Amsterdam Institute for Infection and Immunity, Cancer Immunology, Amsterdam, Netherlands
Besenius, Pol (författare)
Department of Chemistry, Johannes Gutenberg University Mainz, Duesbergweg 10−14, Mainz, Germany
Westerlind, Ulrika (författare)
Umeå universitet,Kemiska institutionen
Murphy, Paul V. (författare)
School of Biological and Chemical Sciences, University of Galway, University Rd., Galway, Ireland; SSPC, The Science Foundation Ireland Research Centre for Pharmaceuticals, University of Galway, University Rd., Galway, Ireland
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School of Biological and Chemical Sciences, University of Galway, University Rd, Galway, Ireland; Department of Chemistry, Johannes Gutenberg University Mainz, Duesbergweg 10−14, Mainz, Germany Institute of Immunology, University Medical Center Mainz, Langenbeckstr.1, Mainz, Germany (creator_code:org_t)
American Chemical Society (ACS), 2023
2023
Engelska.
Ingår i: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 0002-7863 .- 1520-5126. ; 145:24, s. 13027-13037
Relaterad länk:
https://doi.org/10.1...
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https://umu.diva-por... (primary) (Raw object)
https://urn.kb.se/re...
https://doi.org/10.1...
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  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
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  • Mucin expression and glycosylation patterns on cancer cells differ markedly from healthy cells. Mucin 1 (MUC1) is overexpressed in several solid tumors and presents high levels of aberrant, truncated O-glycans (e.g., Tn antigen). Dendritic cells (DCs) express lectins that bind to these tumor-associated carbohydrate antigens (TACAs) to modulate immune responses. Selectively targeting these receptors with synthetic TACAs is a promising strategy to develop anticancer vaccines and to overcome TACA tolerance. In this work, we prepared, via a solid phase peptide synthesis approach, a modular tripartite vaccine candidate, incorporating a high-affinity glycocluster based on a tetraphenylethylene scaffold, to target the macrophage galactose-type lectin (MGL) on antigen presenting cells. MGL is a C-type lectin receptor that binds Tn antigens and can route them to human leukocyte antigen class II or I, making it an attractive target for anticancer vaccines. Conjugation of the glycocluster to a library of MUC1 glycopeptides bearing the Tn antigen is shown to promote uptake and recognition of the TACA by DCs via MGL. In vivo testing revealed that immunization with the newly designed vaccine construct bearing the GalNAc glycocluster induced a higher titer of anti-Tn-MUC1 antibodies compared to the TACAs alone. Additionally, the antibodies obtained bind a library of tumor-associated saccharide structures on MUC1 and MUC1-positive breast cancer cells. Conjugation of a high-affinity ligand for MGL to tumor-associated MUC1 glycopeptide antigens has a synergistic impact on antibody production.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Andra medicinska och farmaceutiska grundvetenskaper (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Other Basic Medicine (hsv//eng)

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