Biparatopic antibodies: therapeutic applications and prospects

Autor: David L. Niquille, Kyle M. Fitzgerald, Nimish Gera
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: mAbs, Vol 16, Iss 1 (2024)
Druh dokumentu: article
ISSN: 19420862
1942-0870
1942-0862
DOI: 10.1080/19420862.2024.2310890
Popis: ABSTRACTBiparatopic 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.
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