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Plant cell-made protein antigens for induction of Oral tolerance.

Authors
  • Daniell, Henry1
  • Kulis, Michael2
  • Herzog, Roland W3
  • 1 Department of Biochemistry, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: [email protected]
  • 2 Department of Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
  • 3 Department of Pediatrics, Indiana University, Indianapolis, IN 46202, USA. Electronic address: [email protected] , (India)
Type
Published Article
Journal
Biotechnology advances
Publisher
Oxford : Pergamon Press
Publication Date
Nov 15, 2019
Volume
37
Issue
7
Pages
107413–107413
Identifiers
DOI: 10.1016/j.biotechadv.2019.06.012
PMID: 31251968
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

The gut associated lymphoid tissue has effective mechanisms in place to maintain tolerance to food antigens. These can be exploited to induce antigen-specific tolerance for the prevention and treatment of autoimmune diseases and severe allergies and to prevent serious immune responses in protein replacement therapies for genetic diseases. An oral tolerance approach for the prevention of peanut allergy in infants proved highly efficacious and advances in treatment of peanut allergy have brought forth an oral immunotherapy drug that is currently awaiting FDA approval. Several other protein antigens made in plant cells are in clinical development. Plant cell-made proteins are protected in the stomach from acids and enzymes after their oral delivery because of bioencapsulation within plant cell wall, but are released to the immune system upon digestion by gut microbes. Utilization of fusion protein technologies facilitates their delivery to the immune system, oral tolerance induction at low antigen doses, resulting in efficient induction of FoxP3+ and latency-associated peptide (LAP)+ regulatory T cells that express immune suppressive cytokines such as IL-10. LAP and IL-10 expression represent potential biomarkers for plant-based oral tolerance. Efficacy studies in hemophilia dogs support clinical development of oral delivery of bioencapsulated antigens to prevent anti-drug antibody formation. Production of clinical grade materials in cGMP facilities, stability of antigens in lyophilized plant cells for several years when stored at ambient temperature, efficacy of oral delivery of human doses in large animal models and lack of toxicity augur well for clinical advancement of this novel drug delivery concept. Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.

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