Oral tolerance to prevent anti-drug antibody formation in protein replacement therapies.
Anti-drug antibody
Enzyme replacement therapy
FIX
FVIII
Hemophilia
IL-10
LAP
Oral tolerance
Pompe disease
Tregs
Journal
Cellular immunology
ISSN: 1090-2163
Titre abrégé: Cell Immunol
Pays: Netherlands
ID NLM: 1246405
Informations de publication
Date de publication:
12 2022
12 2022
Historique:
received:
21
09
2022
revised:
07
11
2022
accepted:
09
11
2022
pubmed:
20
11
2022
medline:
7
12
2022
entrez:
19
11
2022
Statut:
ppublish
Résumé
Protein based therapeutics have successfully improved the quality of life for patients of monogenic disorders like hemophilia, Pompe and Fabry disease. However, a significant proportion of patients develop immune responses towards intravenously infused therapeutic protein, which can complicate or neutralize treatment and compromise patient safety. Strategies aimed at circumventing immune responses following therapeutic protein infusion can greatly improve therapeutic efficacy. In recent years, antigen-based oral tolerance induction has shown promising results in the prevention and treatment of autoimmune diseases, food allergies and can prevent anti-drug antibody formation to protein replacement therapies. Oral tolerance exploits regulatory mechanisms that are initiated in the gut associated lymphoid tissue (GALT) to promote active suppression of orally ingested antigen. In this review, we outline general perceptions and current knowledge about the mechanisms of oral tolerance, including tissue specific sites of tolerance induction and the cells involved, with emphasis on antigen presenting cells and regulatory T cells. We define several factors, such as cytokines and metabolites that impact the stability and expansion potential of these immune modulatory cells. We highlight preclinical studies that have been performed to induce oral tolerance to therapeutic proteins or enzymes for single gene disorders, such as hemophilia or Pompe disease. These studies mainly utilize a transgenic plant-based system for oral delivery of antigen in conjugation with fusion protein technology that favors the prevention of antigen degradation in the stomach while enhancing uptake in the small intestine by antigen presenting cells and regulatory T cell induction, thereby promoting antigen specific systemic tolerance.
Identifiants
pubmed: 36402002
pii: S0008-8749(22)00166-6
doi: 10.1016/j.cellimm.2022.104641
pmc: PMC9730862
mid: NIHMS1851133
pii:
doi:
Substances chimiques
Antibodies
0
Types de publication
Review
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
104641Subventions
Organisme : NHLBI NIH HHS
ID : R01 HL133191
Pays : United States
Informations de copyright
Copyright © 2022 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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