Therapeutic Proteins
Top Cited Papers
- 24 May 2012
- book chapter
- Published by Springer Nature
- Vol. 899, 1-26
- https://doi.org/10.1007/978-1-61779-921-1_1
Abstract
Protein-based therapeutics are highly successful in clinic and currently enjoy unprecedented recognition of their potential. More than 100 genuine and similar number of modified therapeutic proteins are approved for clinical use in the European Union and the USA with 2010 sales of US$108 bln; monoclonal antibodies (mAbs) accounted for almost half (48%) of the sales. Based on their pharmacological activity, they can be divided into five groups: (a) replacing a protein that is deficient or abnormal; (b) augmenting an existing pathway; (c) providing a novel function or activity; (d) interfering with a molecule or organism; and (e) delivering other compounds or proteins, such as a radionuclide, cytotoxic drug, or effector proteins. Therapeutic proteins can also be grouped based on their molecular types that include antibody-based drugs, Fc fusion proteins, anticoagulants, blood factors, bone morphogenetic proteins, engineered protein scaffolds, enzymes, growth factors, hormones, interferons, interleukins, and thrombolytics. They can also be classified based on their molecular mechanism of activity as (a) binding non-covalently to target, e.g., mAbs; (b) affecting covalent bonds, e.g., enzymes; and (c) exerting activity without specific interactions, e.g., serum albumin. Most protein therapeutics currently on the market are recombinant and hundreds of them are in clinical trials for therapy of cancers, immune disorders, infections, and other diseases. New engineered proteins, including bispecific mAbs and multispecific fusion proteins, mAbs conjugated with small molecule drugs, and proteins with optimized pharmacokinetics, are currently under development. However, in the last several decades, there are no conceptually new methodological developments comparable, e.g., to genetic engineering leading to the development of recombinant therapeutic proteins. It appears that a paradigm change in methodologies and understanding of mechanisms is needed to overcome major challenges, including resistance to therapy, access to targets, complexity of biological systems, and individual variations.Keywords
This publication has 65 references indexed in Scilit:
- Shortened Engineered Human Antibody CH2 Domains: INCREASED STABILITY AND BINDING TO THE HUMAN NEONATAL Fc RECEPTOR*Journal of Biological Chemistry, 2011
- Bifunctional fusion proteins of the human engineered antibody domain m36 with human soluble CD4 are potent inhibitors of diverse HIV-1 isolatesAntiviral Research, 2010
- A large library based on a novel (CH2) scaffold: Identification of HIV-1 inhibitorsBiochemical and Biophysical Research Communications, 2009
- Engineered Human Antibody Constant Domains with Increased StabilityPublished by Elsevier ,2009
- CTLA-4 blockade enhances polyfunctional NY-ESO-1 specific T cell responses in metastatic melanoma patients with clinical benefitProceedings of the National Academy of Sciences, 2008
- Therapeutic Antibodies: Current State and Future Trends – Is a Paradigm Change Coming Soon?Published by Springer Nature ,2008
- Directing cancer cells to self-destruct with pro-apoptotic receptor agonistsNature Reviews Drug Discovery, 2008
- Human domain antibodies to conserved sterically restricted regions on gp120 as exceptionally potent cross-reactive HIV-1 neutralizersProceedings of the National Academy of Sciences, 2008
- Construction of a Large Phage-Displayed Human Antibody Domain Library with a Scaffold Based On a Newly Identified Highly Soluble, Stable Heavy Chain Variable DomainJournal of Molecular Biology, 2008
- Cross-reactive HIV-1 neutralizing monoclonal antibodies selected by screening of an immune human phage library against an envelope glycoprotein (gp140) isolated from a patient (R2) with broadly HIV-1 neutralizing antibodiesVirology, 2007