Induction of Tolerance to Therapeutic Proteins With Antigen-Processing Independent T Cell Epitopes: Controlling Immune Responses to Biologics

The immune response to exogenous proteins can overcome the therapeutic benefits of immunotherapies and hamper the treatment of protein replacement therapies. One clear example of this is haemophilia A resulting from deleterious mutations in the FVIII gene. Replacement with serum derived or recombina...

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Bibliographic Details
Published in:Frontiers in immunology 2021-09, Vol.12, p.742695-742695
Main Authors: Schurgers, Evelien, Wraith, David C
Format: Article
Language:English
Subjects:
Antigen Presentation - immunology
Biological Products - immunology
Epitopes, T-Lymphocyte - immunology
haemophilia A
Humans
hypersensitivity
Immune Tolerance - immunology
Immunological tolerance
Immunology
immunotherapy
Immunotherapy - adverse effects
Tr1 cell
Treg cell
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Summary:The immune response to exogenous proteins can overcome the therapeutic benefits of immunotherapies and hamper the treatment of protein replacement therapies. One clear example of this is haemophilia A resulting from deleterious mutations in the FVIII gene. Replacement with serum derived or recombinant FVIII protein can cause anti-drug antibodies in 20-50% of individuals treated. The resulting inhibitor antibodies override the benefit of treatment and, at best, make life unpredictable for those treated. The only way to overcome the inhibitor issue is to reinstate immunological tolerance to the administered protein. Here we compare the various approaches that have been tested and focus on the use of antigen-processing independent T cell epitopes (apitopes) for tolerance induction. Apitopes are readily designed from any protein whether this is derived from a clotting factor, enzyme replacement therapy, gene therapy or therapeutic antibody.
ISSN:1664-3224
1664-3224
DOI:10.3389/fimmu.2021.742695