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Cavaco M, Gaspar D, Arb Castanho M, et al. Antibodies for the Treatment of Brain Metastases, a Dream or a Reality?. Pharmaceutics. 2020;12(1)doi: 10.3390/pharmaceutics12010062.
Cavaco, M., Gaspar, D., Arb Castanho, M., & Neves, V. (2020). Antibodies for the Treatment of Brain Metastases, a Dream or a Reality?. Pharmaceutics, 12(1), . https://doi.org/10.3390/pharmaceutics12010062
Cavaco, Marco, et al. "Antibodies for the Treatment of Brain Metastases, a Dream or a Reality?." Pharmaceutics vol. 12,1 (2020). doi: https://doi.org/10.3390/pharmaceutics12010062
Cavaco M, Gaspar D, Arb Castanho M, Neves V. Antibodies for the Treatment of Brain Metastases, a Dream or a Reality?. Pharmaceutics. 2020 Jan 13;12(1). doi: 10.3390/pharmaceutics12010062. PMID: 31940974; PMCID: PMC7023012.
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Pharmaceutics. 2020 Jan 13;12(1). doi: 10.3390/pharmaceutics12010062.

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

Pharmaceutics

Marco Cavaco, Diana Gaspar, Miguel Arb Castanho, Vera Neves

Affiliations

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

PMID: 31940974 PMCID: PMC7023012 DOI: 10.3390/pharmaceutics12010062

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.

Keywords: adsorptive-mediated transcytosis; antibody fragments; blood–brain barrier; brain metastases; monoclonal antibodies; peptide shuttles

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