Advances in cancer research have led to the development of new therapeutics with significant and durable responses such as immune checkpoint inhibitors. More recent therapies aim to stimulate anti-tumor immune responses by targeting the tumor necrosis factor (TNF) receptors, however this approach has been shown to require clustering of receptors in order to achieve a significant response. Here we present a perspective on using transthyretin, a naturally occurring serum protein, as a drug delivery platform to enable cross-linking independent clustering of targets. TTR forms a stable homo-tetramer with exposed termini that make TTR a highly versatile platform for generating multimeric antibody fusions to enable enhanced target clustering. Fusions with antibodies or Fabs targeting TRAILR2 were shown to have robust cytotoxic activity in vitro and in vivo in colorectal xenograft models demonstrating that TTR is a highly versatile, stable, therapeutic fusion platform that can be used with antibodies, Fabs and other bioactive fusion partners and has broad applications in oncology and infectious disease research.
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November 2021
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This special issue of Emerging Topics in Life Sciences (volume 5, issue 5) brings together a collection of perspectives about innovative techniques and ideas from scientists working in the life sciences industry. The cover image is an illustration featured in the piece discussing by ImmTOR™ by Brunn and Kishimoto.
Perspective|
July 20 2021
Transthyretin-mediated protein and peptide oligomerization for enhanced target clustering
Daniel Yoo;
Daniel Yoo
Amgen Research, Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA 91320, U.S.A
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Kenneth W. Walker
Amgen Research, Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA 91320, U.S.A
Correspondence: Kenneth W. Walker (kennethw@amgen.com)
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Publisher: Portland Press Ltd
Received:
May 06 2021
Revision Received:
June 24 2021
Accepted:
June 28 2021
Online ISSN: 2397-8562
Print ISSN: 2397-8554
© 2021 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society and the Royal Society of Biology
2021
Emerg Top Life Sci (2021) 5 (5): 665–668.
Article history
Received:
May 06 2021
Revision Received:
June 24 2021
Accepted:
June 28 2021
Citation
Daniel Yoo, Kenneth W. Walker; Transthyretin-mediated protein and peptide oligomerization for enhanced target clustering. Emerg Top Life Sci 12 November 2021; 5 (5): 665–668. doi: https://doi.org/10.1042/ETLS20210028
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