Multispecific antibodies to improved efficacy and safety and to reduce costs for CNS immunotherapy

Purpose and goal

The project´s aim is to improve immunotherapy for diseases of the CNS by increasing the uptake in the brain of therapeutic antibodies. By fusing the antibodies with a transporter for targeted passage across the blood-brain barrier via binding to the human transferrin receptor (TfR), we have succeeded in demonstrating an increased brain exposure and faster binding to the disease target (Abeta) for therapeutic antibodies in a transgenic Alzheimer´s mouse model. We have also studied bispecific antibodies of different formats with regard to uptake and distribution in the brain.

Expected results and effects

Proof of concept studies have been carried out in a mouse model with successful results as both improved brain uptake and improved effect have been shown. The technology can be used to treat various diseases of the brain with high efficacy and improved safety.

Planned approach and implementation

Antibodies against TfR were produced by hybridoma technique. New methods for visualization and quantification of antibody uptake and distribution in the brain have been developed. Selected antibodies have been fused to therapeutic antibodies in various bispecific formats. Brain uptake and disease-modifying effects have been analyzed in mouse models. This has provided new knowledge on how antibodies get into the brain and how uptake can be influenced by an intelligent protein design. This is expected to be of great importance for the development of new drugs for brain disorders.