Synthetically glycosylated antigens for the antigen-specific suppression of established immune responses.

Autor: Tremain AC; Committee on Immunology, University of Chicago, Chicago, IL, USA., Wallace RP; Pritzker School for Molecular Engineering, University of Chicago, Chicago, IL, USA., Lorentz KM; Anokion US Inc., Cambridge, MA, USA., Thornley TB; Anokion US Inc., Cambridge, MA, USA., Antane JT; Pritzker School for Molecular Engineering, University of Chicago, Chicago, IL, USA., Raczy MR; Pritzker School for Molecular Engineering, University of Chicago, Chicago, IL, USA., Reda JW; Pritzker School for Molecular Engineering, University of Chicago, Chicago, IL, USA., Alpar AT; Pritzker School for Molecular Engineering, University of Chicago, Chicago, IL, USA., Slezak AJ; Pritzker School for Molecular Engineering, University of Chicago, Chicago, IL, USA., Watkins EA; Pritzker School for Molecular Engineering, University of Chicago, Chicago, IL, USA., Maulloo CD; Pritzker School for Molecular Engineering, University of Chicago, Chicago, IL, USA., Budina E; Pritzker School for Molecular Engineering, University of Chicago, Chicago, IL, USA., Solanki A; Animal Resources Center, University of Chicago, Chicago, IL, USA., Nguyen M; Animal Resources Center, University of Chicago, Chicago, IL, USA., Bischoff DJ; Anokion US Inc., Cambridge, MA, USA., Harrington JL; Anokion US Inc., Cambridge, MA, USA., Mishra R; Anokion US Inc., Cambridge, MA, USA., Conley GP; Anokion US Inc., Cambridge, MA, USA., Marlin R; Center for Immunology of Viral, Auto-immune, Hematological and Bacterial Diseases (IMVA-HB/IDMIT), Université Paris-Saclay, INSERM, CEA, Fontenay-aux-Roses, France., Dereuddre-Bosquet N; Center for Immunology of Viral, Auto-immune, Hematological and Bacterial Diseases (IMVA-HB/IDMIT), Université Paris-Saclay, INSERM, CEA, Fontenay-aux-Roses, France., Gallouët AS; Center for Immunology of Viral, Auto-immune, Hematological and Bacterial Diseases (IMVA-HB/IDMIT), Université Paris-Saclay, INSERM, CEA, Fontenay-aux-Roses, France., LeGrand R; Center for Immunology of Viral, Auto-immune, Hematological and Bacterial Diseases (IMVA-HB/IDMIT), Université Paris-Saclay, INSERM, CEA, Fontenay-aux-Roses, France., Wilson DS; Pritzker School for Molecular Engineering, University of Chicago, Chicago, IL, USA. scott.wilson@jhmi.edu.; Biomedical Engineering Department, Johns Hopkins University, Baltimore, MD, USA. scott.wilson@jhmi.edu., Kontos S; Anokion US Inc., Cambridge, MA, USA., Hubbell JA; Committee on Immunology, University of Chicago, Chicago, IL, USA. jhubbell@uchicago.edu.; Pritzker School for Molecular Engineering, University of Chicago, Chicago, IL, USA. jhubbell@uchicago.edu.; Committee on Cancer Biology, University of Chicago, Chicago, IL, USA. jhubbell@uchicago.edu.
Jazyk: angličtina
Zdroj: Nature biomedical engineering [Nat Biomed Eng] 2023 Sep; Vol. 7 (9), pp. 1142-1155. Date of Electronic Publication: 2023 Sep 07.
DOI: 10.1038/s41551-023-01086-2
Abstrakt: Inducing antigen-specific tolerance during an established immune response typically requires non-specific immunosuppressive signalling molecules. Hence, standard treatments for autoimmunity trigger global immunosuppression. Here we show that established antigen-specific responses in effector T cells and memory T cells can be suppressed by a polymer glycosylated with N-acetylgalactosamine (pGal) and conjugated to the antigen via a self-immolative linker that allows for the dissociation of the antigen on endocytosis and its presentation in the immunoregulatory environment. We show that pGal-antigen therapy induces antigen-specific tolerance in a mouse model of experimental autoimmune encephalomyelitis (with programmed cell-death-1 and the co-inhibitory ligand CD276 driving the tolerogenic responses), as well as the suppression of antigen-specific responses to vaccination against a DNA-based simian immunodeficiency virus in non-human primates. Our findings show that pGal-antigen therapy invokes mechanisms of immune tolerance to resolve antigen-specific inflammatory T-cell responses and suggest that the therapy may be applicable across autoimmune diseases.
(© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)
Databáze: MEDLINE
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