Mechanism-Driven Design of Multispecific Antibodies for Targeted Disease Treatment

doi:10.1146/annurev-chembioeng-100522-102155

Review

. 2024 Jan 26.

doi: 10.1146/annurev-chembioeng-100522-102155. Online ahead of print.

Mechanism-Driven Design of Multispecific Antibodies for Targeted Disease Treatment

Justyn Fine^{1

2}, Bunyarit Meksiriporn^{2

3

4}, Jiacheng Tan^{2

3}, Jamie B Spangler^{2

3

5

6

7}

Affiliations

¹ Program in Molecular Biophysics, Johns Hopkins University, Baltimore, Maryland 21208, USA.
² Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA; email: jamie.spangler@jhu.edu.
³ Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
⁴ Department of Biology, School of Science, King Mongkut's Institute of Technology Ladkrabang, Bangkok 10520, Thailand.
⁵ Department of Chemical & Biomolecular Engineering, Johns Hopkins University School of Engineering, Baltimore, Maryland, USA.
⁶ Departments of Oncology, Opthalmology, and Molecular Microbiology and Immunology, Bloomberg-Kimmel Institute for Cancer Immunotherapy, and Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
⁷ Department of Molecular Microbiology and Immunology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USA.

PMID: 38277673
DOI: 10.1146/annurev-chembioeng-100522-102155

Free article

Review

Mechanism-Driven Design of Multispecific Antibodies for Targeted Disease Treatment

Justyn Fine et al. Annu Rev Chem Biomol Eng. 2024.

Free article

. 2024 Jan 26.

doi: 10.1146/annurev-chembioeng-100522-102155. Online ahead of print.

Authors

Justyn Fine^{1

2}, Bunyarit Meksiriporn^{2

3

4}, Jiacheng Tan^{2

3}, Jamie B Spangler^{2

3

5

6

7}

Affiliations

¹ Program in Molecular Biophysics, Johns Hopkins University, Baltimore, Maryland 21208, USA.
² Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA; email: jamie.spangler@jhu.edu.
³ Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
⁴ Department of Biology, School of Science, King Mongkut's Institute of Technology Ladkrabang, Bangkok 10520, Thailand.
⁵ Department of Chemical & Biomolecular Engineering, Johns Hopkins University School of Engineering, Baltimore, Maryland, USA.
⁶ Departments of Oncology, Opthalmology, and Molecular Microbiology and Immunology, Bloomberg-Kimmel Institute for Cancer Immunotherapy, and Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
⁷ Department of Molecular Microbiology and Immunology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USA.

PMID: 38277673
DOI: 10.1146/annurev-chembioeng-100522-102155

Abstract

Antibody-based therapeutics constitute a rapidly growing class of pharmaceutical compounds. However, monoclonal antibodies, which specifically engage only one target, often lack the mechanistic intricacy to treat complex diseases. To expand the utility of antibody therapies, significant efforts have been invested in designing multispecific antibodies, which engage multiple targets using a single molecule. These efforts have culminated in remarkable translational progress, including nine US Food and Drug Administration-approved multispecific antibodies, with countless others in various stages of preclinical or clinical development. In this review, we discuss several categories of multispecific antibodies that have achieved clinical approval or shown promise in earlier stages of development. We focus on the molecular mechanisms used by multispecific antibodies and how these mechanisms inform their customized design and formulation. In particular, we discuss multispecific antibodies that target multiple disease markers, multiparatopic antibodies, and immune-interfacing antibodies. Overall, these innovative multispecific antibody designs are fueling exciting advances across the immunotherapeutic landscape. Expected final online publication date for the Annual Review of Chemical and Biomolecular Engineering , Volume 15 is June 2024. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

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Mechanism-Driven Design of Multispecific Antibodies for Targeted Disease Treatment

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Mechanism-Driven Design of Multispecific Antibodies for Targeted Disease Treatment

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