Thursday, February 20, 2014
Publication and contact
Improved brain delivery of
anti-transferrin receptor (TFRC;
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.
Published online Feb. 20, 2014
Patent and licensing status
Bien-Ly, N. et al. J.
Exp. Med.; published online Jan. 27, 2014;
Contact: Ryan J. Watts, Genentech Inc., South San Francisco,
Contact: Inhee Chung, same affiliation as above
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