Multimeric antibodies with increased valency surpassing functional affinity and potency thresholds using novel formats.
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Publication Date
2020-01ICR Author
Author
Miller, A
Carr, S
Rabbitts, T
Ali, H
Type
Journal Article
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Show full item recordAbstract
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.
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Licenseref URL
https://creativecommons.org/licenses/by-nc/4.0Version of record
Research team
Chromosomal Translocations and Intracellular Antibody Therapeutics
Language
eng
License start date
2020-01
Citation
mAbs, 2020, 12 (1), pp. 1752529 - ?