Recombinant Human Serum Albumin Fusion Proteins and Novel Applications in Drug Delivery and Therapy

Abstract

Fusion proteins have been well-studied and widely applied in biopharmaceutics. Albumin fusion proteins are simple to construct, easy to purify, and stable to formulate. One main application of fusion protein is to extend the plasma half-life of therapeutic proteins and peptides. Albiglutide for diabetes treatment is the first albumin fusion protein drug approved by FDA. Balugrastim and other albumin fusion proteins have been evaluated in clinical trials. Taking advantage of the physiological functions of albumin, albumin fusion proteins can also been applied to act on an essential intracellular target and carry fatty acid-modified drugs. This novel approach makes it possible to co-deliver two different types of drug to one tumor cell for synergistic cytotoxicity.

Engineering potent long-acting variants of the Wnt inhibitor DKK2

“…HSA has many desirable pharmaceutical properties. These include a serum half-life of 19–20 days; solubility of ~300 mg/ml; good stability; ease of expression; no effector function; low immunogenicity and circulating serum levels of ~45 mg/ml (Rogers et al ., 2015). The crystal structure of HSA with and without ligands, including biologically important molecules such as fatty acids and drugs, or in complex with other proteins is well documented (He and Carter, 1992; Sugio et al ., 1999).…”

“…HSA was chosen as the fusion platform for DKK2C2 because of its desirable pharmacological attributes such as its long-lived nature, high solubility and stability in serum, and its lack of immune reactivity. The effectiveness of HSA to improve the aforementioned properties of its fusion partner has been previously demonstrated with the glucagon-like peptide-1 agonist albiglutide, the first albumin fusion protein drug approved by the FDA in 2014, and other albumin fusion proteins currently in clinical trials (Rogers et al ., 2015). As part of the optimization of the HSA-DKK2C2 construct, we varied the length of the linker sequence from within DKK2 connecting HSA with the C2 domain; HSA-DKK2C2 (H174-I259) was selected for all subsequent studies.…”

New developments in the treatment of chemotherapy-induced neutropenia: focus on balugrastim

“…A new generation of long-acting rG-CSFs has been recently developed by combining G-CSF with a protein or peptide (fusion proteins) in order to increase molecular weight and lengthen t 1/2 . 21 Balugrastim is a long-acting rG-CSF produced in the yeast Saccharomyces cerevisiae obtained by means of a genetic fusion between recombinant human serum albumin and G-CSF. 21 , 22 By combining the N-terminus of G-CSF to the C-terminus of albumin, balugrastim has a high plasmatic stability and can be administered in a once-per-cycle fixed dosage.…”

“… 21 Balugrastim is a long-acting rG-CSF produced in the yeast Saccharomyces cerevisiae obtained by means of a genetic fusion between recombinant human serum albumin and G-CSF. 21 , 22 By combining the N-terminus of G-CSF to the C-terminus of albumin, balugrastim has a high plasmatic stability and can be administered in a once-per-cycle fixed dosage. 21 So far, few studies have investigated balugrastim’s safety and activity.…”

“… 21 , 22 By combining the N-terminus of G-CSF to the C-terminus of albumin, balugrastim has a high plasmatic stability and can be administered in a once-per-cycle fixed dosage. 21 So far, few studies have investigated balugrastim’s safety and activity. This review aims at summarizing the available literature data on this novel molecule, focusing on pharmacology, pharmacokinetics, toxicity, and efficacy.…”