Switchable assembly and function of antibody complexes in vivo using a small molecule-Reference-Cited by-同舟云学术

Switchable assembly and function of antibody complexes in vivo using a small molecule

Published:2022-02-24 Issue:9 Volume:119 Page:
ISSN:0027-8424
Container-title:Proceedings of the National Academy of Sciences
language:en
Short-container-title:Proc. Natl. Acad. Sci. U.S.A.

Author:

Martinko Alexander J.¹^ORCID,Simonds Erin F.¹,Prasad Suchitra¹,Ponce Alberto¹,Bracken Colton J.²^ORCID,Wei Junnian³,Wang Yung-Hua³,Chow Tiffany-Lynn¹,Huang Zhong¹,Evans Michael J.³^ORCID,Wells James A.⁴⁵^ORCID,Hill Zachary B.¹

Affiliation:

1. Department of Research and Development, Soteria Biotherapeutics, Inc., San Mateo, CA 94403

2. Chemistry and Chemical Biology Graduate Program, University of California, San Francisco, CA 94107

3. Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA 94107

4. Department of Pharmaceutical Chemistry, University of California, San Francisco, CA 94107

5. Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94107

Abstract

Significance Reported here, we describe a molecular protein technology to enable switchable assembly of functional antibody complexes. This approach, which we call ligand-induced transient engagement (LITE), allows for control of an antibody’s intended function in vivo through the dosing of a small-molecule activator. Chemical regulation of antibody therapeutics represents a treatment paradigm to provide physicians with precise control over the therapeutic activity of a biologic drug after it is administered to a patient. Ultimately, this approach may result in a new class of antibody drugs with improved efficacy and safety profiles and the potential to greatly impact the treatment of human disease.

Publisher

Proceedings of the National Academy of Sciences

Subject

Multidisciplinary

Link

https://pnas.org/doi/pdf/10.1073/pnas.2117402119

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