Biparatopic antibodies: therapeutic applications and prospects

Biparatopic antibodies (bpAbs) bind distinct, non-overlapping epitopes on an antigen. This unique binding mode enables new mechanisms of action beyond monospecific and bispecific antibodies (bsAbs) that can make bpAbs effective therapeutics for various indications, including oncology and infectious...

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Bibliographic Details
Published in:mAbs 2024-12, Vol.16 (1), p.2310890
Main Authors: Niquille, David L., Fitzgerald, Kyle M., Gera, Nimish
Format: Article
Language:English
Subjects:
Antibodies, Bispecific - therapeutic use
Antibody engineering
antibody-drug conjugates
biparatopic antibodies
bispecific antibodies
chimeric antigen receptors
Epitopes
Immunoconjugates
infectious disease
oncology
Receptors, Chimeric Antigen
Review
T-cell engagers
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Summary:Biparatopic antibodies (bpAbs) bind distinct, non-overlapping epitopes on an antigen. This unique binding mode enables new mechanisms of action beyond monospecific and bispecific antibodies (bsAbs) that can make bpAbs effective therapeutics for various indications, including oncology and infectious diseases. Biparatopic binding can lead to superior affinity and specificity, promote antagonism, lock target conformation, and result in higher-order target clustering. Such antibody-target complexes can elicit strong agonism, increase immune effector function, or result in rapid target downregulation and lysosomal trafficking. These are not only attractive properties for therapeutic antibodies but are increasingly being explored for other modalities such as antibody-drug conjugates, T-cell engagers and chimeric antigen receptors. Recent advances in bpAb engineering have enabled the construction of ever more sophisticated formats that are starting to show promise in the clinic.
ISSN:1942-0862
1942-0870
1942-0870
DOI:10.1080/19420862.2024.2310890