AACR 2023: Discovery of RenNano®-Derived Human Heavy-Chain-Only Antibodies That Cross the Blood-Brain-Barrier

Conclusions

• TFR1-targeting HCAbs developed from RenNano® mice have high affinity to human TFR1, and have functional capabilities, including internalization capacity.
• hTFR1-targeting HCAbs are able to penetrate the BBB efficiently, as evidenced by fractionation studies and histological analyses.
• Together, these data highlight the tremendous potential for HCAbs and its variable domain sdAbs for transporting cargo across the BBB. Due to their smaller size and simpler structure, sdAbs could ultimately provide therapeutic benefit for neurodegenerative diseases, and offer promising potential for tumor penetration.