دورية أكاديمية
Multimeric antibodies with increased valency surpassing functional affinity and potency thresholds using novel formats
| العنوان: | Multimeric antibodies with increased valency surpassing functional affinity and potency thresholds using novel formats |
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| المؤلفون: | Ami Miller, Stephen Carr, Terry Rabbitts, Hanif Ali |
| المصدر: | mAbs, Vol 12, Iss 1 (2020) |
| بيانات النشر: | Taylor & Francis Group, 2020. |
| سنة النشر: | 2020 |
| المجموعة: | LCC:Therapeutics. Pharmacology LCC:Immunologic diseases. Allergy |
| مصطلحات موضوعية: | Multivalent, antibody, tetravalent, octavalent, avidity, bispecific, Therapeutics. Pharmacology, RM1-950, Immunologic diseases. Allergy, RC581-607 |
| الوصف: | The success of therapeutic antibodies is largely attributed for their exquisite specificity, homogeneity, and functionality. There is, however, a need to engineer antibodies to extend and enhance their potency. One parameter is functional affinity augmentation, since antibodies matured in vivo have a natural affinity threshold. Generation of multivalent antibodies is one option capable of surpassing this affinity threshold through increased avidity. In this study, we present a novel platform consisting of an array of multivalent antibody formats, termed Quads, generated using the self-assembling tetramerization domain from p53. We demonstrate the versatility of this tetramerization domain by engineering anti-tumor necrosis factor (TNF) Quads that exhibit major increases in binding potency and in neutralizing TNF-mediated cytotoxicity compared to parental anti-TNF molecules. Further, Quads are amenable to fusion with different binding domains, allowing generation of novel multivalent monospecific and bispecific formats. Quads are thus a novel group of molecules that can be engineered to yield potential therapeutics with novel modalities and potencies. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 19420862 1942-0870 1942-0862 |
| Relation: | https://doaj.org/toc/1942-0862; https://doaj.org/toc/1942-0870 |
| DOI: | 10.1080/19420862.2020.1752529 |
| URL الوصول: | https://doaj.org/article/56130f5d71b041afb82a98ac8bbb0b0f |
| رقم الأكسشن: | edsdoj.56130f5d71b041afb82a98ac8bbb0b0f |
| قاعدة البيانات: | Directory of Open Access Journals |
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Full Text Finder | تدمد: | 19420862 19420870 |
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| DOI: | 10.1080/19420862.2020.1752529 |