Brain Disposition of Antibody-Based Therapeutics: Dogma, Approaches and Perspectives
Abstract
:1. Introduction
2. Delivery of Antibodies into the Brain: Mechanism of Delivery
2.1. Physiology and Barriers of the CNS
2.2. BBB Structure
2.3. Pharmacokinetics and CNS Distribution of Antibodies
2.4. Mechanisms of Antibody Passage Across the BBB
3. Current In Vitro and In Vivo Methodologies for Measuring Brain Access of Antibodies: Advantages and Limitations
3.1. In Vitro Methods
3.2. In Vivo Methods
4. Approaches to Optimize BBB Internalization and Uptake of Antibodies
4.1. Modification of BBB Permeability
4.2. Physiological Approach to Transport Antibodies Across the BBB
4.3. Antibody Engineering Approaches to Increase Trans-BBB Transport
4.3.1. Role of Fc Receptors
4.3.2. Role of Antigen Binding
4.3.3. Role of Biophysical Properties
5. Conclusions and Outlook
Author Contributions
Funding
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Kouhi, A.; Pachipulusu, V.; Kapenstein, T.; Hu, P.; Epstein, A.L.; Khawli, L.A. Brain Disposition of Antibody-Based Therapeutics: Dogma, Approaches and Perspectives. Int. J. Mol. Sci. 2021, 22, 6442. https://doi.org/10.3390/ijms22126442
Kouhi A, Pachipulusu V, Kapenstein T, Hu P, Epstein AL, Khawli LA. Brain Disposition of Antibody-Based Therapeutics: Dogma, Approaches and Perspectives. International Journal of Molecular Sciences. 2021; 22(12):6442. https://doi.org/10.3390/ijms22126442
Chicago/Turabian StyleKouhi, Aida, Vyshnavi Pachipulusu, Talya Kapenstein, Peisheng Hu, Alan L. Epstein, and Leslie A. Khawli. 2021. "Brain Disposition of Antibody-Based Therapeutics: Dogma, Approaches and Perspectives" International Journal of Molecular Sciences 22, no. 12: 6442. https://doi.org/10.3390/ijms22126442