Ab locks for improving the selectivity and safety of antibody drugs
Abstract Monoclonal antibodies (mAbs) are a major targeted therapy for malignancies, infectious diseases, autoimmune diseases, transplant rejection and chronic inflammatory diseases due to their antigen specificity and longer half-life than conventional drugs. However, long-term systemic antigen neu...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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BMC
2020-06-01
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| Series: | Journal of Biomedical Science |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12929-020-00652-z |
| _version_ | 1818995323786231808 |
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| author | Wen-Wei Lin Yun-Chi Lu Chih-Hung Chuang Tian-Lu Cheng |
| author_facet | Wen-Wei Lin Yun-Chi Lu Chih-Hung Chuang Tian-Lu Cheng |
| author_sort | Wen-Wei Lin |
| collection | DOAJ |
| description | Abstract Monoclonal antibodies (mAbs) are a major targeted therapy for malignancies, infectious diseases, autoimmune diseases, transplant rejection and chronic inflammatory diseases due to their antigen specificity and longer half-life than conventional drugs. However, long-term systemic antigen neutralization by mAbs may cause severe adverse events. Improving the selectivity of mAbs to distinguish target antigens at the disease site from normal healthy tissue and reducing severe adverse events caused by the mechanisms-of-action of mAbs is still a pressing need. Development of pro-antibodies (pro-Abs) by installing a protease-cleavable Ab lock is a novel and advanced recombinant Ab-based strategy that efficiently masks the antigen binding ability of mAbs in the normal state and selectively “turns on” the mAb activity when the pro-Ab reaches the proteolytic protease-overexpressed diseased tissue. In this review, we discuss the design and advantages/disadvantages of different Ab lock strategies, focusing particularly on spatial-hindrance-based and affinity peptide-based approaches. We expect that the development of different masking strategies for mAbs will benefit the local reactivity of mAbs at the disease site, increase the therapeutic efficacy and safety of long-term treatment with mAbs in chronic diseases and even permit scientists to develop Ab drugs for formerly undruggable targets and satisfy the unmet medical needs of mAb therapy. |
| first_indexed | 2024-12-20T21:12:01Z |
| format | Article |
| id | doaj.art-683231de7fa74837b659cda00e6f7b17 |
| institution | Directory Open Access Journal |
| issn | 1423-0127 |
| language | English |
| last_indexed | 2024-12-20T21:12:01Z |
| publishDate | 2020-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Biomedical Science |
| spelling | doaj.art-683231de7fa74837b659cda00e6f7b172022-12-21T19:26:30ZengBMCJournal of Biomedical Science1423-01272020-06-0127112010.1186/s12929-020-00652-zAb locks for improving the selectivity and safety of antibody drugsWen-Wei Lin0Yun-Chi Lu1Chih-Hung Chuang2Tian-Lu Cheng3Department of Laboratory Medicine, School of Medicine, College of Medicine, Kaohsiung Medical UniversityDrug Development and Value Creation Research Center, Kaohsiung Medical UniversityGraduate Institute of Medicine, College of Medicine, Kaohsiung Medical UniversityGraduate Institute of Medicine, College of Medicine, Kaohsiung Medical UniversityAbstract Monoclonal antibodies (mAbs) are a major targeted therapy for malignancies, infectious diseases, autoimmune diseases, transplant rejection and chronic inflammatory diseases due to their antigen specificity and longer half-life than conventional drugs. However, long-term systemic antigen neutralization by mAbs may cause severe adverse events. Improving the selectivity of mAbs to distinguish target antigens at the disease site from normal healthy tissue and reducing severe adverse events caused by the mechanisms-of-action of mAbs is still a pressing need. Development of pro-antibodies (pro-Abs) by installing a protease-cleavable Ab lock is a novel and advanced recombinant Ab-based strategy that efficiently masks the antigen binding ability of mAbs in the normal state and selectively “turns on” the mAb activity when the pro-Ab reaches the proteolytic protease-overexpressed diseased tissue. In this review, we discuss the design and advantages/disadvantages of different Ab lock strategies, focusing particularly on spatial-hindrance-based and affinity peptide-based approaches. We expect that the development of different masking strategies for mAbs will benefit the local reactivity of mAbs at the disease site, increase the therapeutic efficacy and safety of long-term treatment with mAbs in chronic diseases and even permit scientists to develop Ab drugs for formerly undruggable targets and satisfy the unmet medical needs of mAb therapy.http://link.springer.com/article/10.1186/s12929-020-00652-zMonoclonal antibody (mAb)adverse eventsAb lockspatial-hindrance-based approachesaffinity-based approaches |
| spellingShingle | Wen-Wei Lin Yun-Chi Lu Chih-Hung Chuang Tian-Lu Cheng Ab locks for improving the selectivity and safety of antibody drugs Journal of Biomedical Science Monoclonal antibody (mAb) adverse events Ab lock spatial-hindrance-based approaches affinity-based approaches |
| title | Ab locks for improving the selectivity and safety of antibody drugs |
| title_full | Ab locks for improving the selectivity and safety of antibody drugs |
| title_fullStr | Ab locks for improving the selectivity and safety of antibody drugs |
| title_full_unstemmed | Ab locks for improving the selectivity and safety of antibody drugs |
| title_short | Ab locks for improving the selectivity and safety of antibody drugs |
| title_sort | ab locks for improving the selectivity and safety of antibody drugs |
| topic | Monoclonal antibody (mAb) adverse events Ab lock spatial-hindrance-based approaches affinity-based approaches |
| url | http://link.springer.com/article/10.1186/s12929-020-00652-z |
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