Engineered antibody fusion proteins for targeted disease therapy

Aliyah B Silver; Elissa K Leonard; Joseph R Gould; Jamie B Spangler

doi:10.1016/j.tips.2021.09.009

Engineered antibody fusion proteins for targeted disease therapy

Trends Pharmacol Sci. 2021 Dec;42(12):1064-1081. doi: 10.1016/j.tips.2021.09.009. Epub 2021 Oct 25.

Authors

Aliyah B Silver¹, Elissa K Leonard², Joseph R Gould², Jamie B Spangler³

Affiliations

¹ Department of Molecular Microbiology and Immunology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA; Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
² Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
³ Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD, USA; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Bloomberg-Kimmel Institute for Cancer Immunotherapy, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Ophthalmology, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA. Electronic address: [email protected].

Abstract

Since the FDA approval of the first therapeutic antibody 35 years ago, antibody-based products have gained prominence in the pharmaceutical market. Building on the early successes of monoclonal antibodies, more recent efforts have capitalized on the exquisite specificity and/or favorable pharmacokinetic properties of antibodies by developing fusion proteins that enable targeted delivery of therapeutic payloads which are otherwise ineffective when administered systemically. This review focuses on recent engineering and translational advances for therapeutics that genetically fuse antibodies to disease-relevant payloads, including cytokines, toxins, enzymes, neuroprotective agents, and soluble factor traps. With numerous antibody fusion proteins in the clinic and other innovative molecules poised to follow suit, these potent, multifunctional drug candidates promise to be a major player in the therapeutic development landscape for years to come.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Review

MeSH terms

Antibodies, Monoclonal*
Cytokines*
Humans

Substances

Antibodies, Monoclonal
Cytokines

Abstract

Publication types

MeSH terms

Substances

Grants and funding