Passage of Humanized Monoclonal Antibodies Across the Blood-Brain Barrier: Relevance in the Treatment of Cancer Brain Metastases?

Therapeutic monoclonal antibodies have widely contributed to improving survival in metastatic cancers. However, patients are at increased risk of developing central nervous system metastases, and the survival of patients with brain metastases remains poor, challenging daily practice in medical oncology. The mechanisms limiting the use of therapeutic monoclonal antibodies for the treatment of brain tumours are their inadequate transport from blood to brain, and a probable efflux from brain to blood by way of endothelial cell transporters like the FcRn receptor. In this review, we set out to discuss published data on experimental studies on the transport across the blood-brain-barrier of monoclonal antibodies in one or other direction. We will summarize what has been achieved with commercialized antibodies, and discuss future developments for the treatment of brain metastases in cancer patients using humanized monoclonal antibodies.