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Biologics

Transferrin' bispecific antibodies across the blood–brain barrier

Nature Reviews Drug Discovery volume 14, pages 14–15 (2015) Cite this article

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First, the authors generated a humanized TFR-specific antibody (anti-TFR1) that binds to the receptor at a site distant from its ligand-binding sites. A modified version of anti-TFR1 that had 20–25-fold lower affinity for TFR — anti-TFR2 — was also created to assess the impact of TFR affinity on brain uptake. Next, using 'knobs into holes' technology (in which a large amino acid is substituted for a small one in the heavy chain of one half-antibody to create the 'knob' and vice versa in another half-antibody to create the 'hole'), the authors created two types of heterodimeric antibodies, anti-TFR1–BACE and anti-TFR2–BACE, each of which had one anti-TFR arm and one BACE-specific arm.

Both types of antibody led to a 55–65% reduction of Aβ levels in the plasma and in the brain of these animals

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References

  1. Yu, Y. J. et al. Therapeutic bispecific antibodies cross the blood–brain barrier in nonhuman primates. Sci. Transl Med. 6, 261ra154 (2014)

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  1. Natasha Bray
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Garber, K. Bispecific antibodies rise again. Nature Rev. Drug Discov. 13, 799–801 (2014)

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Bray, N. Transferrin' bispecific antibodies across the blood–brain barrier. Nat Rev Drug Discov 14, 14–15 (2015). https://doi.org/10.1038/nrd4522

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