Antibodies for the Treatment of Brain Metastases, a Dream or a Reality?

Pharmaceutics

Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Av. Prof. Egas Moniz, 1649-028 Lisboa, Portugal.

Published: January 2020

AI Article Synopsis

  • - The incidence of brain metastases in cancer patients is rising, but survival rates remain low due to ineffective treatments, particularly for CNS tumors. - Monoclonal antibodies (mAbs) are effective for treating various cancers but struggle to penetrate the blood-brain barrier (BBB), which limits their use against CNS tumors. - Researchers are investigating the use of BBB peptide shuttles as a solution to enhance the delivery of mAbs to the brain, allowing for better targeting and treatment of metastatic brain cells.

Article Abstract

The incidence of brain metastases (BM) in cancer patients is increasing. After diagnosis, overall survival (OS) is poor, elicited by the lack of an effective treatment. Monoclonal antibody (mAb)-based therapy has achieved remarkable success in treating both hematologic and non-central-nervous system (CNS) tumors due to their inherent targeting specificity. However, the use of mAbs in the treatment of CNS tumors is restricted by the blood-brain barrier (BBB) that hinders the delivery of either small-molecules drugs (sMDs) or therapeutic proteins (TPs). To overcome this limitation, active research is focused on the development of strategies to deliver TPs and increase their concentration in the brain. Yet, their molecular weight and hydrophilic nature turn this task into a challenge. The use of BBB peptide shuttles is an elegant strategy. They explore either receptor-mediated transcytosis (RMT) or adsorptive-mediated transcytosis (AMT) to cross the BBB. The latter is preferable since it avoids enzymatic degradation, receptor saturation, and competition with natural receptor substrates, which reduces adverse events. Therefore, the combination of mAbs properties (e.g., selectivity and long half-life) with BBB peptide shuttles (e.g., BBB translocation and delivery into the brain) turns the therapeutic conjugate in a valid approach to safely overcome the BBB and efficiently eliminate metastatic brain cells.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7023012PMC
http://dx.doi.org/10.3390/pharmaceutics12010062DOI Listing

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