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Improved brain delivery of anti-transferrin receptor (TFRC; TFR)-containing antibodies by reducing TFRC affinity

Mouse studies suggest lowering anti-TFRC antibody affinity could increase brain uptake of blood brain barrier (BBB)-penetrant, bispecific antibodies. In mice, a bispecific, anti-TFRC and anti-b-amyloid cleaving enzyme 1 (BACE1) antibody with low affinity for TFRC led to increased surface-expressed Tfrc levels on BBB endothelial cells and increased BBB trafficking and brain uptake compared with a related antibody with high affinity for TFRC. This relative increase in surface-expressed Tfrc was seen because the low-affinity antibody induced less lysosome-mediated degradation of Tfrc than the high-affinity antibody. Ongoing work includes validating the approach in nonhuman primates.

SciBX 7(7); doi:10.1038/scibx.2014.209
Published online Feb. 20, 2014

Patent and licensing status undisclosed

Bien-Ly, N. et al. J. Exp. Med.; published online Jan. 27, 2014;
Contact: Ryan J. Watts, Genentech Inc., South San Francisco, Calif.
Contact: Inhee Chung, same affiliation as above