Preclinical B cell depletion and safety profile of a brain-shuttled crystallizable fragment-silenced CD20 antibody.

ABSTRACT:

Background

The blood-brain barrier (BBB) presents a major challenge for the development of monoclonal antibody (mAb)-based therapies for brain disorders. To improve the likelihood of success of such therapies, Roche Brainshuttle technology utilizes a single anti-transferrin receptor 1 (TfR1)-antigen-binding antibody fragment linked to a therapeutic antibody, allowing engagement with TfR1 to transport the therapeutic antibody into the brain via receptor-mediated transcytosis.

Methods

We compared Fc-silenced and Fc-competent variants of the Brainshuttle and the parental (non-shuttled) type II CD20 mAb, obinutuzumab in in vitro and in vivo (mouse and cynomolgus macaque) models. Endpoints assessed included B cell binding, B cell killing, tolerability, and ability to cross the BB

SUBMITTER: Schumacher VL 

PROVIDER: S-EPMC11928292 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature