On receiving the Best Poster Award
We are pleased to announce that we received the Best Poster Award at the 37th Annual Meeting of the Japanese Society of Pharmacokinetics for the presentation of “Transport characteristics of genetically engineered BBB-permeable cyclic peptide-conjugated monoclonal antibody in vitro and in vivo” at the 37th Annual Meeting of the Japanese Society of Pharmacokinetics. I am very honored to receive the prestigious Best Poster Award for the presentation entitled “Transport characteristics of genetically engineered BBB-permeable cyclic peptide-conjugated monoclonal antibody in vitro and in vivo. I would like to take this opportunity to express my sincere gratitude to the selection committee members and all the people involved in the Japanese Society of Pharmacokinetics and Pharmacodynamics.
In recent years, monoclonal antibodies have shown promise as therapeutic agents for the treatment of central nervous system diseases with low treatment satisfaction. However, the transferability of monoclonal antibodies to the brain is extremely low due to the barrier function of the blood-brain barrier (BBB), leading to failure of clinical trials, side effects caused by high-dose administration, and an increased burden on the medical economy. Therefore, we aim to establish a fundamental technology to facilitate the delivery of monoclonal antibodies into the brain through the BBB. Previously, our laboratory identified a BBB-permeable cyclic peptide, the SLS peptide, which enables the permeation of macromolecular compounds through the BBB (Yamaguchi, et al. 2020). In this study, we evaluated the in vitro BBB permeation and in vivo brain distribution of SLS-expressing antibodies, in which SLS peptides were genetically engineered to be expressed at the C-terminus of the H-chain of a monoclonal antibody.
First, we measured the intracellular uptake of SLS-expressing antibodies in vitro using hCMEC/D3, a human brain capillary endothelial cell model, and rat BBB model cells, and observed a significant increase in uptake compared to non-expressing antibodies. Next, we evaluated the brain translocation of each antibody by in vivo experiments using mice. The amount of SLS-expressing antibody in the brain at 1 hour post-dose was significantly 6-fold higher than that of non-expressing antibody. These results suggest that the expression of SLS peptide can promote the migration of monoclonal antibodies into the brain via the BBB. The method established in this study can be applied to any monoclonal antibody, since existing monoclonal antibody production technology can be used without modification. The results of this research are expected to contribute to the development of antibody drugs for central nervous system diseases.
Finally, we would like to take this opportunity to express our sincere gratitude to Associate Professor Shingo Ito and all the faculty members and students in our laboratory who have been our main supervisors in conducting this research.