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The Scientific Basis of Medicine
Published in John S. Axford, Chris A. O'Callaghan, Medicine for Finals and Beyond, 2023
Chris O'Callaghan, Rachel Allen
The high specificity of monoclonal antibodies for antigens has led to their development as precision therapeutics to block protein interactions, prevent receptor signalling, or label their targets for destruction. Antibody-based therapies are now the dominant class of biopharmaceuticals and are used to treat a variety of diseases. When new therapeutic targets are identified, antibodies can provide a rapid route to modifying their functions. Monoclonal antibody treatments have proved particularly effective in the treatment of rheumatoid arthritis, where the inflammatory cytokines TNF-alpha and IL-6 are important mediators of disease pathogenesis. Biologic disease-modifying antirheumatic drugs include monoclonal antibodies specific for TNF-alpha, IL-6 and the receptor for IL-6 (see Chapter 4, Rheumatic disease). Recombinant proteins can also be used as therapeutics. For example, the drug anakinra is a modified form of the IL-1 receptor antagonist used for the treatment of rheumatoid arthritis. Disadvantages of such therapies include their high cost and potential to increase susceptibility to infections such as tuberculosis.
Polymer-Based Protein Delivery Systems for Loco-Regional Administration
Published in Richard L. K. Glover, Daniel Nyanganyura, Rofhiwa Bridget Mulaudzi, Maluta Steven Mufamadi, Green Synthesis in Nanomedicine and Human Health, 2021
Muhammad Haji Mansor, Emmanuel Garcion, Bathabile Ramalapa, Nela Buchtova, Clement Toullec, Marique Aucamp, Jean Le Bideau, François Hindré, Admire Dube, Carmen Alvarez-Lorenzo, Moreno Galleni, Christine Jérôme, Frank Boury
Recombinant production of proteins is highly favoured over purification of proteins from their native source. A small number of non-recombinant proteins purified from their native source have been reported, such as pancreatic enzymes from hog and pig pancreas (Dirksen et al., 1999) and alpha-1 proteinase inhibitor from pooled human plasma (Yamaguchi and Miyazaki, 2014). This strategy however has proven to be rather challenging and expensive. In this regard, the production of therapeutic proteins by genetic engineering using recombinant DNA technology has presented great opportunities towards overcoming the challenges faced with conventional non-recombinant proteins. In addition to availability in sufficient quantities and the reduced risk of immunological rejection, recombinant technology allows the modification of proteins or the selection of particular gene variants to improve function or specificity and enables the production of proteins that provide novel functions or activity (Banting et al., 1991). Thus, modern therapeutic proteins are largely produced by recombinant technology.
The Immune System and Immune Modulation
Published in Thomas F. Kresina, Immune Modulating Agents, 2020
François Hirsch, Guido Kroemer
In clinical and outpatient routine, immunomodulatory interventions nowadays are still limited to rather few approaches. However, medical practice will soon be enriched by the availability of an increasing amount of sophisticated tools for immunomodulation. On the one hand, recombinant gene technology allows the generation of recombinant proteins. On the other hand, gene therapy may facilitate novel, previously inconceivable types of immunomodulation. As a caveat, it should be noted that both increasing costs and practical obstacles will limit the use of these novel types of immunomodulation to severe diseases of the economically privileged classes in Western countries. Therefore, the search for simple chemicals for immune therapy should not be abandoned at the expense of recombinant proteins or DNA-based molecules. Whatever the future will bring to us, it appears clear, however, that any kind of immunomodulation will have to take into account the three existential choices made by B and T cells, as defined earlier: survival versus death, response versus anergy, and different classes of response. Therefore, the succesful development of immunomodulatory regimens will depend critically on the fundamental understanding of the immune system.
Interplay of heavy chain introns influences efficient transcript splicing and affects product quality of recombinant biotherapeutic antibodies from CHO cells
Published in mAbs, 2023
Emma Kelsall, Claire Harris, Titash Sen, Diane Hatton, Sarah Dunn, Suzanne Gibson
High-yielding recombinant protein expression is fundamental for biopharmaceutical production. Monoclonal antibodies (mAbs), which occupy a substantial fraction of the total biotherapeutic market, are predominantly produced in heterologous expression systems of mammalian origin such as Chinese hamster ovary (CHO) cells.1 As product heterogeneity can arise between manufacturing batches,2 regulatory guidelines require critical quality attributes (CQA) to be monitored.3,4 For mAbs, CQAs include the protein primary structure, variants of which can result in altered antibody structure that, in turn, can affect potency, pharmacokinetics, and product safety.5,6 Therefore, identifying and characterizing any sequence variants present is essential during product development.
Current status of COVID-19 vaccination: safety and liability concern for children, pregnant and lactating women
Published in Expert Review of Vaccines, 2022
Swagat Kumar Das, Manish Paul, Bikash Chandra Behera, Hrudayanath Thatoi
Each vaccine platform comes with its own set of benefits and drawbacks. Nucleic acid vaccines, for example, are easier to design than protein vaccines, but they induce less immunity. Furthermore, as compared to other vaccines, mRNA vaccines are considered unstable. Similarly, viral vector and subunit vaccines are regarded safe and have more immunogenicity than other vaccinations, although they have lower efficacy and are more expensive [24]. In the case of recombinant protein vaccines, no infectious virus is utilized, and adjuvants are used to boost immunogenicity. However, the disadvantage of this type of vaccine development is that the global production capacity is limited. Antigen or epitope integrity must be validated throughout adjuvant development. There is no need to handle infectious viruses if a non-replicating viral vector is used in vaccine development. This sort of vaccine research has also produced excellent and promising preclinical and clinical results for numerous new viruses, including MERS-CoV.
Fluorescent quantum dots enable SARS-CoV-2 antiviral drug discovery and development
Published in Expert Opinion on Drug Discovery, 2022
Kirill Gorshkov, Kimihiro Susumu, Mason Wolak, Eunkeu Oh
Despite the great utility of QD bioconjugation for antiviral research, the work is limited by the quality and character of the recombinant protein used for conjugation. Our work relies on recombinant proteins from commercial vendors. Because S trimers are found in viral particles, conjugating S trimers to QDs would provide the most physiologically relevant model rather than a monomer, subunit, or domain. However, recombinant S trimers are challenging to produce. To stabilize the proteins, several mutations can be introduced to yield sufficiently intact and properly folded proteins. Some of these stabilizing mutations abolish the cleavage site of furin proteases that process the precursor S, and others are found at the TMPRSS2 site. Care must be taken to confirm the purity of the proteins used and the mutations introduced into S. Further, given the different routes of entry SARS-CoV-2 can take, either fusion at the membrane when TMPRSS2 is present and active, or endocytosis via ACE2, it is possible inhibition of one route of entry can shunt the virus toward using the other route of entry. In the case of our QD-RBD, only the endocytic route of entry is available for study.