Biotherapeutics are transforming the health care landscape through new ways of treating diseases that were previously complex in severity, thus improving outcomes in patients. Protein drugs represent one of the major research and development areas in the field of biotherapeutics, owing to their wide applications in the targeted therapies of hard-to-treat diseases.
Biotherapeutics, also referred to as biologics, are drugs that are produced from living organisms or their cells. Protein drugs, as a key subclass of therapeutic proteins, are designed to interact specifically with biological pathways in the body.. (5)
Insulin, discovered almost a century ago, was the advent of protein drugs and one of the most important events in the history of medicine. (1) Today, it includes monoclonal antibodies (mAbs), cytokines, fusion proteins, among others, with gigantic expansion into the scope and variety of protein therapeutics. (2)
Today, protein drugs are a cornerstone of protein therapy, revolutionizing treatments for cancer, autoimmune diseases, and genetic disorders by acting only on disease-specific molecules, hence reducing side effects and opening the doors to personalized medicine. Specificity, potency, and versatility have allowed these drugs to gain a foothold within the wider therapeutic arsenal and to offer new hopes to patients with conditions that were previously difficult to treat. (3-5)
The therapeutic effect of protein-based drugs is created by selective interaction with cellular targets modulating biological processes. This makes them useful in treating chronic inflammatory and autoimmune diseases. (5) Consequently, proteins also tend to be highly specific, with reduced activity against off-targets, compared to small-molecule drugs. These complex natures of the three-dimensional structure confer higher-order functions, including receptor blocking and immune modulation-important in the treatment of diseases such as cancer and autoimmune disorders. The promising land for such medications toward personalized therapy comprises the growing demand for biotherapeutics in a number of therapeutic fields, including oncology, immunology, and endocrinology. (5, 6) Fast growth in the pharmaceutical industry and the contributions of leading biotherapeutics companies place protein drugs as pivotal solutions for addressing unmet medical needs. (4)
Protein drugs are very heterogeneous therapeutic products because of the diverse actions and applications. Below are some of the most common in this dynamic field:
Protein drugs are changing the face of treatment in many areas, since they have specific advantages over conventional small-molecule drugs. Due to their highly target-specific natures, FDA approved protein drugs offer minimal off-target effects, hence limited side effects and a particularly appropriate feasibility for long-term administration. (5) Their reduced toxicity is highly important in areas such as oncology, where protecting healthy cells is critical; the biocompatibility-with structures similar to natural proteins-means there are fewer side effects, and the body can process it without major risks of refusal or serious immune response. (8)
On the other hand, protein drugs face a different set of challenges. Due to their inherent tendency to aggregate, degrade, or denature, proteins usually have short half-lives, which often equate to short half times and frequent dosing or special formulations. Immunogenicity is another challenge, although researchers are working on structural modifications in efforts to improve tolerance. Common approaches being used include PEGylation, glycosylation, lipidation, and protein fusion, all with the goal of increasing stability and reducing immune responses. (5)
Production of therapeutic proteins is also not straightforward. Many protein therapeutics, including mAbs and fusion proteins, may be over 100 kDa, making the chemical synthesis technically difficult. They are to be produced in living cells, which indicates that factors like cell line option, species origin, and conditions of cultivation highly influence the features of the final product. Such complex characteristics in various proteins make many of the recombinant production strategies inefficiently yield poor products or generate purified products which have no functionality due to non-conserved conformations. (5)
In order to meet the challenges presented by the production of these molecules, Numaferm developed Numaswitch®, a platform technology for high-efficiency, large-scale production of peptide and protein therapeutics. Central to this technology is a reagent called the Switchtag, a bivalent protein tag. Fusion with a protein of interest yields a fusion protein that forms aggregates in E. coli cells; this acts to protect the target protein against proteolytic degradation. As observed, Switchtags are refolding tags that, upon extraction, ensure correct refolding of target proteins with a calcium ion and hence preserve the secondary and tertiary structures of proteins required for protein function. Employment of such technology has greatly simplified the production of high-quality protein drugs for a number of therapeutic applications. (9,10)
The bio-therapeutic horizon is, therefore, rapidly evolving where protein-based drugs have emerged as the new game changers for the treatment of several complex diseases. With further advances in protein engineering and recombinant DNA technology, these therapeutics offer solutions tailored to the required needs with improved efficacy and fewer side effects. Research is still continuing despite all the challenges associated with production and stability, and new technologies such as Numaswitch® point to better manufacturing processes. The future of biotherapeutics looks great, and protein drugs have been expanding this therapeutic armory and bring new hope to the previously hopeless patient.