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...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-09-01
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| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2021.742695/full |
| _version_ | 1818608105092546560 |
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| author | Evelien Schurgers David C. Wraith |
| author_facet | Evelien Schurgers David C. Wraith |
| author_sort | Evelien Schurgers |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-16T14:37:21Z |
| format | Article |
| id | doaj.art-7b43f812124949209e9936a832697c09 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-16T14:37:21Z |
| publishDate | 2021-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-7b43f812124949209e9936a832697c092022-12-21T22:28:04ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-09-011210.3389/fimmu.2021.742695742695Induction of Tolerance to Therapeutic Proteins With Antigen-Processing Independent T Cell Epitopes: Controlling Immune Responses to BiologicsEvelien Schurgers0David C. Wraith1Apitope International NV, Diepenbeek, BelgiumInstitute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United KingdomThe 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.https://www.frontiersin.org/articles/10.3389/fimmu.2021.742695/fullImmunological tolerancehaemophilia ATr1 cellTreg cellimmunotherapyhypersensitivity |
| spellingShingle | Evelien Schurgers David C. Wraith Induction of Tolerance to Therapeutic Proteins With Antigen-Processing Independent T Cell Epitopes: Controlling Immune Responses to Biologics Frontiers in Immunology Immunological tolerance haemophilia A Tr1 cell Treg cell immunotherapy hypersensitivity |
| title | Induction of Tolerance to Therapeutic Proteins With Antigen-Processing Independent T Cell Epitopes: Controlling Immune Responses to Biologics |
| title_full | Induction of Tolerance to Therapeutic Proteins With Antigen-Processing Independent T Cell Epitopes: Controlling Immune Responses to Biologics |
| title_fullStr | Induction of Tolerance to Therapeutic Proteins With Antigen-Processing Independent T Cell Epitopes: Controlling Immune Responses to Biologics |
| title_full_unstemmed | Induction of Tolerance to Therapeutic Proteins With Antigen-Processing Independent T Cell Epitopes: Controlling Immune Responses to Biologics |
| title_short | Induction of Tolerance to Therapeutic Proteins With Antigen-Processing Independent T Cell Epitopes: Controlling Immune Responses to Biologics |
| title_sort | induction of tolerance to therapeutic proteins with antigen processing independent t cell epitopes controlling immune responses to biologics |
| topic | Immunological tolerance haemophilia A Tr1 cell Treg cell immunotherapy hypersensitivity |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2021.742695/full |
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