Denali’s brain delivery method; plus CAR T cell therapy combo and more

Denali Therapeutics Inc. (NASDAQ:DNLI) and collaborators at  University of California San Diego developed a method to enhance delivery of large molecule therapeutics into the CNS by targeting the blood-brain barrier-expressed receptor SLC3A2. The authors of the Nature Communications article fused an engineered SLC3A2 protein to an antibody Fab fragment, creating a new type of antibody transport vehicle (ATV), and examined systemic clearance, brain uptake kinetics, CNS biodistribution and peripheral safety after chronic dosing in mice and non-human primates.

Results showed SLC3A2 ATVs have differentiated properties compared with transferrin receptor-based ATVs, a target that Denali and others are using as an entry point into the CNS, such as slower uptake, more prolonged brain exposure and a distinct brain biodistribution pattern restricted to subsets of glial cells. The complementarity of the platforms “provides an opportunity to tailor platform selection based on cell type-specific therapeutic targeting and desired mechanisms of action,” said the authors...