Bispecific antibodies for delivery into the brain

• The blood–brain barrier restricts drug delivery to the brain.
• Endogenous brain endothelial transport pathways exist.
• The transferrin receptor (TfR) pathway can be utilized for drug delivery.
• Weak affinity for the TfR can enable antibody release into brain.
• Bispecific antibodies can facilitates transport and provide therapeutic benefit.

The blood–brain barrier (BBB) is a formidable obstacle preventing drug delivery to the brain, particularly for large protein therapeutics. The utilization of endogenous brain endothelial transport pathways, however, represents a promising approach to cross the cellular barrier through receptor-mediated transcytosis. Therapeutics designed to take advantage of this approach require at least two functionalities, one that facilitates transport and the other to provide therapeutic benefit, and bispecific antibodies are ideally suited for this task.