Anticalin® proteins: from bench to bedside

Structural plasticity in the loop region of engineered lipocalins with novel ligand specificities, so-called Anticalins

“…Compared with Igs, with their large size (∼1500 residues), a complicated quaternary structure and complex disulfide bridge and glycosylation patterns, the small and robust lipocalin proteins simply comprise a single polypeptide chain of approximately 180 amino acid residues. This offers several benefits, such as much easier biochemical manipulation and recombinant production as well as the facile construction of fusion proteins incorporating additional functions ( Deuschle et al, 2021 , Richter et al, 2014 ). To minimize undesired immunogenicity upon administration to patients, human lipocalins were chosen as appropriate scaffolds for protein engineering in this context, in particular the human lipocalin 1 (Lcn1), also known as tear lipocalin, and the human lipocalin 2 (Lcn2), also known as neutrophil gelatinase-associated lipocalin or siderocalin ( Schiefner and Skerra, 2015 ).…”

“…To minimize undesired immunogenicity upon administration to patients, human lipocalins were chosen as appropriate scaffolds for protein engineering in this context, in particular the human lipocalin 1 (Lcn1), also known as tear lipocalin, and the human lipocalin 2 (Lcn2), also known as neutrophil gelatinase-associated lipocalin or siderocalin ( Schiefner and Skerra, 2015 ). Several promising Anticalin drug candidates exhibiting specificities towards different medically relevant target proteins, mainly in the areas of oncology and inflammatory diseases, were generated in this manner and are currently subject to clinical studies at various stages ( Deuschle et al, 2021 , Rothe and Skerra, 2018 ).…”

Kidney Cancer and Chronic Kidney Disease: Too Close for Comfort

“…An advantage of these synthetic peptides is their small size relative to conventional monoclonal antibodies (about 1/8 of the size). This fact explains anticalins’ improved tissue penetration properties, benefiting drug delivery and better clearance properties and minimizing potential side-effects due to prolonged exposures [ 79 ]. In a first-in-human trial involving RCC patients, an anti-VEGF anticalin effectively rendered VEGF undetectable in systemic circulation [ 80 ].…”

Monobodies as tool biologics for accelerating target validation and druggable site discovery

“…Among numerous synthetic binding protein platforms, the most established systems include designed ankyrin repeat proteins (DARPins), 72,[85][86][87] monobodies, 88,89 anticalins, [90][91][92] and affibodies. [93][94][95] Numerous binding proteins, or "binders", have been derived from "natural" scaffolds of antibody fragments such as single-chain variable fragment (scFv) and nanobodies.…”