Multimeric antibodies with increased valency surpassing functional affinity and potency thresholds using novel formats.
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ICR Authors
Authors
Miller, A
Carr, S
Rabbitts, T
Ali, H
Carr, S
Rabbitts, T
Ali, H
Document Type
Journal Article
Date
2020-01-01
Date Accepted
Abstract
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.
Citation
mAbs, 2020, 12 (1), pp. 1752529 - ?
Source Title
Publisher
TAYLOR & FRANCIS INC
ISSN
1942-0862
eISSN
1942-0870
Collections
Research Team
Chromosomal Translocations and Intracellular Antibody Therapeutics