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      Development of therapeutic antibodies for the treatment of diseases

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          Abstract

          It has been more than three decades since the first monoclonal antibody was approved by the United States Food and Drug Administration (US FDA) in 1986, and during this time, antibody engineering has dramatically evolved. Current antibody drugs have increasingly fewer adverse effects due to their high specificity. As a result, therapeutic antibodies have become the predominant class of new drugs developed in recent years. Over the past five years, antibodies have become the best-selling drugs in the pharmaceutical market, and in 2018, eight of the top ten bestselling drugs worldwide were biologics. The global therapeutic monoclonal antibody market was valued at approximately US$115.2 billion in 2018 and is expected to generate revenue of $150 billion by the end of 2019 and $300 billion by 2025. Thus, the market for therapeutic antibody drugs has experienced explosive growth as new drugs have been approved for treating various human diseases, including many cancers, autoimmune, metabolic and infectious diseases. As of December 2019, 79 therapeutic mAbs have been approved by the US FDA, but there is still significant growth potential. This review summarizes the latest market trends and outlines the preeminent antibody engineering technologies used in the development of therapeutic antibody drugs, such as humanization of monoclonal antibodies, phage display, the human antibody mouse, single B cell antibody technology, and affinity maturation. Finally, future applications and perspectives are also discussed.

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          The blockade of immune checkpoints in cancer immunotherapy.

          Among the most promising approaches to activating therapeutic antitumour immunity is the blockade of immune checkpoints. Immune checkpoints refer to a plethora of inhibitory pathways hardwired into the immune system that are crucial for maintaining self-tolerance and modulating the duration and amplitude of physiological immune responses in peripheral tissues in order to minimize collateral tissue damage. It is now clear that tumours co-opt certain immune-checkpoint pathways as a major mechanism of immune resistance, particularly against T cells that are specific for tumour antigens. Because many of the immune checkpoints are initiated by ligand-receptor interactions, they can be readily blocked by antibodies or modulated by recombinant forms of ligands or receptors. Cytotoxic T-lymphocyte-associated antigen 4 (CTLA4) antibodies were the first of this class of immunotherapeutics to achieve US Food and Drug Administration (FDA) approval. Preliminary clinical findings with blockers of additional immune-checkpoint proteins, such as programmed cell death protein 1 (PD1), indicate broad and diverse opportunities to enhance antitumour immunity with the potential to produce durable clinical responses.
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            Pembrolizumab versus Chemotherapy for PD-L1–Positive Non–Small-Cell Lung Cancer

            Pembrolizumab is a humanized monoclonal antibody against programmed death 1 (PD-1) that has antitumor activity in advanced non-small-cell lung cancer (NSCLC), with increased activity in tumors that express programmed death ligand 1 (PD-L1).
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              Axicabtagene Ciloleucel CAR T-Cell Therapy in Refractory Large B-Cell Lymphoma

              In a phase 1 trial, axicabtagene ciloleucel (axi-cel), an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, showed efficacy in patients with refractory large B-cell lymphoma after the failure of conventional therapy.
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                Author and article information

                Contributors
                hcw0928@gate.sinica.edu.tw
                Journal
                J Biomed Sci
                J. Biomed. Sci
                Journal of Biomedical Science
                BioMed Central (London )
                1021-7770
                1423-0127
                2 January 2020
                2 January 2020
                2020
                : 27
                : 1
                Affiliations
                [1 ]ISNI 0000 0001 2287 1366, GRID grid.28665.3f, Institute of Cellular and Organismic Biology, Academia Sinica, ; Taipei, 115 Taiwan
                [2 ]128 Academia Rd., Section 2, Nankang, Taipei, 11529 Taiwan
                Author information
                http://orcid.org/0000-0002-5185-1169
                Article
                592
                10.1186/s12929-019-0592-z
                6939334
                31894001
                24c3a3b8-212f-4ffb-b24d-6f5b97685c2c
                © The Author(s). 2020

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 1 August 2019
                : 18 November 2019
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100004663, Ministry of Science and Technology, Taiwan;
                Award ID: 106-0210-01-15-02
                Award ID: 107-0210-01-19-01
                Award ID: 107-0210-01-19-04
                Award Recipient :
                Categories
                Review
                Custom metadata
                © The Author(s) 2020

                Molecular medicine
                therapeutic antibody,antibody market,humanized antibody,phage display,human antibody mouse,single b cell antibody technology,affinity maturation

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