Open AccessSwitchable assembly and function of antibody complexes in vivo using a small molecule
Author(s) -
Alexander J. Martinko,
Erin F. Simonds,
Suchitra Prasad,
Alberto Ponce,
Colton Bracken,
Junnian Wei,
Sinan Wang,
Tiffany-Lynn Chow,
Zhong Huang,
Michael J. Evans,
James A. Wells,
Z.B. Hill
Publication year - 2022
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2117402119
Subject(s) - in vivo , monoclonal antibody , antibody , small molecule , chemistry , conjugate , fusion protein , antigen , immunoglobulin fab fragments , computational biology , biophysics , combinatorial chemistry , microbiology and biotechnology , biochemistry , biology , immunology , recombinant dna , complementarity determining region , genetics , mathematical analysis , mathematics , gene
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.