Posttranslational Modifications and the Immunogenicity of Biotherapeutics
Whilst the amino acid sequence of a protein is determined by its gene sequence, the final structure and function are determined by posttranslational modifications (PTMs), including quality control (QC) in the endoplasmic reticulum (ER) and during passage through the Golgi apparatus. These processes...
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| Format: | Article |
| Language: | English |
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Wiley
2016-01-01
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| Series: | Journal of Immunology Research |
| Online Access: | http://dx.doi.org/10.1155/2016/5358272 |
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| author | Roy Jefferis |
| author_facet | Roy Jefferis |
| author_sort | Roy Jefferis |
| collection | DOAJ |
| description | Whilst the amino acid sequence of a protein is determined by its gene sequence, the final structure and function are determined by posttranslational modifications (PTMs), including quality control (QC) in the endoplasmic reticulum (ER) and during passage through the Golgi apparatus. These processes are species and cell specific and challenge the biopharmaceutical industry when developing a production platform for the generation of recombinant biologic therapeutics. Proteins and glycoproteins are also subject to chemical modifications (CMs) both in vivo and in vitro. The individual is naturally tolerant to molecular forms of self-molecules but nonself variants can provoke an immune response with the generation of anti-drug antibodies (ADA); aggregated forms can exhibit enhanced immunogenicity and QC procedures are developed to avoid or remove them. Monoclonal antibody therapeutics (mAbs) are a special case because their purpose is to bind the target, with the formation of immune complexes (ICs), a particular form of aggregate. Such ICs may be removed by phagocytic cells that have antigen presenting capacity. These considerations may frustrate the possibility of ameliorating the immunogenicity of mAbs by rigorous exclusion of aggregates from drug product. Alternate strategies for inducing immunosuppression or tolerance are discussed. |
| format | Article |
| id | doaj-art-1fd8798e208a4c0d8f5f837e81f708bd |
| institution | Kabale University |
| issn | 2314-8861 2314-7156 |
| language | English |
| publishDate | 2016-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Immunology Research |
| spelling | doaj-art-1fd8798e208a4c0d8f5f837e81f708bd2025-02-03T01:03:35ZengWileyJournal of Immunology Research2314-88612314-71562016-01-01201610.1155/2016/53582725358272Posttranslational Modifications and the Immunogenicity of BiotherapeuticsRoy Jefferis0Institute of Immunology & Immunotherapy, College of Medical & Dental Sciences, University of Birmingham, Birmingham B15 2TT, UKWhilst the amino acid sequence of a protein is determined by its gene sequence, the final structure and function are determined by posttranslational modifications (PTMs), including quality control (QC) in the endoplasmic reticulum (ER) and during passage through the Golgi apparatus. These processes are species and cell specific and challenge the biopharmaceutical industry when developing a production platform for the generation of recombinant biologic therapeutics. Proteins and glycoproteins are also subject to chemical modifications (CMs) both in vivo and in vitro. The individual is naturally tolerant to molecular forms of self-molecules but nonself variants can provoke an immune response with the generation of anti-drug antibodies (ADA); aggregated forms can exhibit enhanced immunogenicity and QC procedures are developed to avoid or remove them. Monoclonal antibody therapeutics (mAbs) are a special case because their purpose is to bind the target, with the formation of immune complexes (ICs), a particular form of aggregate. Such ICs may be removed by phagocytic cells that have antigen presenting capacity. These considerations may frustrate the possibility of ameliorating the immunogenicity of mAbs by rigorous exclusion of aggregates from drug product. Alternate strategies for inducing immunosuppression or tolerance are discussed.http://dx.doi.org/10.1155/2016/5358272 |
| spellingShingle | Roy Jefferis Posttranslational Modifications and the Immunogenicity of Biotherapeutics Journal of Immunology Research |
| title | Posttranslational Modifications and the Immunogenicity of Biotherapeutics |
| title_full | Posttranslational Modifications and the Immunogenicity of Biotherapeutics |
| title_fullStr | Posttranslational Modifications and the Immunogenicity of Biotherapeutics |
| title_full_unstemmed | Posttranslational Modifications and the Immunogenicity of Biotherapeutics |
| title_short | Posttranslational Modifications and the Immunogenicity of Biotherapeutics |
| title_sort | posttranslational modifications and the immunogenicity of biotherapeutics |
| url | http://dx.doi.org/10.1155/2016/5358272 |
| work_keys_str_mv | AT royjefferis posttranslationalmodificationsandtheimmunogenicityofbiotherapeutics |