Anticalins: An emerging class of novel biologics to treat cancer and other severe diseases

摘要

Anticalins are a novel class of small and robust engineered protein reagents, usually derived from human plasma lipocalins, which offer potential as an alternative to antibodies. While human(ized) antibodies (immunoglobulins) constitute an established class of biotherapeutics today, they also show disadvantages, especially in areas where the fullsize molecular format with its immunological effector function is less relevant. Anticalins have a much smaller size, providing better tissue penetration, and they comprise just a single polypeptide chain, thus offering the efficient preparation of fusion proteins and/or conjugation with payloads or enzymes, even by using simple microbial expression systems. Anticalins with prescribed specificities toward disease-relevant biomolecules -e.g., the proangiogenic vascular endothelial growth factor A (VEGF-A), the tumor vasculature-associated extra-domain B of fibronectin or the deactivating T-cell co-receptor CTLA-4- have been conveniently generated via combinatorial design, using targeted random mutagenesis and phage display selection. The VEGF-specific anticalin (Angiocal?) has completed phase I trials, and the clinical study of another anticalin is currently in preparation, apart from a natural lipocalin from insects that has already reached phase II. Due to their versatility with regard to fusion protein generation and/or conjugation with drugs or radionuclides, anticalins appear as a promising class of nextgeneration biopharmaceuticals for cancer therapy and beyond.