Switchable assembly and function of antibody complexes in vivo using a small molecule.
Alexander J Martinko1, Erin F Simonds1, Suchitra Prasad1
1Department of Research and Development, Soteria Biotherapeutics, Inc., San Mateo, CA 94403.
Summary
This study introduces a novel technology for switchable antibody therapies. Chemically induced dimerization allows dynamic control over antibody function in vivo, offering a new approach to biologic drug development.
Area of Science:
- Biotechnology
- Immunology
- Drug Development
Background:
- Monoclonal antibodies are crucial therapeutics due to their specificity and half-life.
- Current antibody-based therapies are often static, with functions fixed upon irreversible fusion of components.
- Novel formats like antibody-drug conjugates and bispecific antibodies have expanded therapeutic applications.
Purpose of the Study:
- To develop a technology for switchable assembly of functional antibody complexes.
- To enable dynamic control over antibody function in vivo using small molecules.
- To demonstrate this switchable assembly across multiple therapeutic applications.
Main Methods:
- Utilized chemically induced dimerization domains for reversible assembly of antibody complexes.
- Engineered switchable antibody formats for therapeutic applications.
- Administered small molecules to modulate complex assembly and function in vivo.
Main Results:
- Successfully demonstrated switchable assembly of functional antibody complexes in vivo.
- Showcased control over radionuclide-conjugated antibody tumor localization.
- Validated extension of cytokine half-life and activation of bispecific T cell-engaging antibodies.
Conclusions:
- Developed a novel technology for switchable antibody therapeutics.
- This approach allows for dynamic, dose-dependent control of antibody function in vivo.
- Offers a versatile platform for developing next-generation biologic drugs with tunable properties.
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