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Enzyme Kinetics and Drugs as Enzyme Inhibitors
Published in Peter Grunwald, Pharmaceutical Biocatalysis, 2019
Elotuzumab and daratumumab are two relatively new mAbs approved by the FDA in 2015 for treatment of patients with relapsed or refractory MM. Elotuzumab targets directly the glycoprotein receptor SLAMF7 (Signalling Lymphocyte Activation Molecule Family Member 7) that is overexpressed on the surface of myeloma and NK cells but is not found on normal cells. It exerts a dual effect in that it activates NK cells directly and also mediates antibody-dependent cell-mediated cytotoxicity (ADCC) by recruiting activated NK cells on MM cells (Lonial et al., 2015). Daratumumab is a human anti-CD38 IgG1 (κ subclass) antibody. It targets the protein CD38 (also an enzyme that catalyzes the metabolism of cyclic adenosine diphosphate ribose and nicotinic acid adenine dinucleotide phosphate) that is overexpressed on multiple myeloma cells and also expressed on many types of immune cells. Its antimyeloma effect mainly relies on its prominent ADCC and complement-dependent cytotoxicity (CDC) activities (Phipps et al., 2015). This topic is discussed in more detail in Section 21.2.3.4.3.
Bioartificial organs
Published in Ronald L. Fournier, Basic Transport Phenomena in Biomedical Engineering, 2017
The Fc receptor on an IgG molecule bound by the Fab fragments to a cellular antigen also binds to specific receptors on so-called natural killer lymphocytes (NK cells). The NK cells will then be attracted to and destroy the invading cell by the release of toxic substances called perforins (Ojcius et al., 1998). Perforins form channels in the cell membrane of the target cell, making them leak and resulting in the death of the cell. This process is called antibody-dependent cell-mediated cytotoxicity, or ADCC.
Enhancement of anti-TNFα monoclonal antibody production in CHO cells through the use of UCOE and DHFR elements in vector construction and the optimization of cell culture media
Published in Preparative Biochemistry & Biotechnology, 2021
Chinh Chung Doan, Nguyen Quynh Chi Ho, Thi Thuy Nguyen, Thi Phuong Thao Nguyen, Dang Giap Do, Nghia Son Hoang, Thanh Long Le
Adalimumab is a typical tumor necrosis factor-α (TNFα) blocker that has been approved for the treatment of severe rheumatoid arthritis, psoriasis, ankylosing spondylitis, and moderate to severe Crohn’s disease.[1] Adalimumab is the first fully human recombinant monoclonal antibody (mAbTNFα) with a high binding affinity to TNFα.[2,3] Compared to other recombinant monoclonal TNFα antibodies, including etanercept or infliximab, adalimumab has a stronger binding affinity and neutralizes both soluble and transmembrane TNFα; it potentially kills TNFα-expressing cells through antibody-dependent cell-mediated cytotoxicity (ADCC) or/and complement-dependent cytotoxicity (CDC).[2,4–6] Furthermore, adalimumab causes less adverse immunogenic reactions than etanercept or infliximab in humans, making it suitable for the long-term treatment of chronic diseases.[2] Adalimumab has a longer circulation half-life (about 10–20 days) than that of etanercept (about 3–5 days) and infliximab (about 5–9 days). Therefore, patients can conveniently inject adalimumab every other week.[3,7] Among originator drugs, Humira, the brand name of the original adalimumab medicine, is frequently at the top of the selling record,[7] indicating the importance of this prescribed drug.
Cloning, large-scale production and characterization of fusion protein (P-TUFT-ALT-2) of Brugian abundant larval transcript-2 with tuftsin in Pichia pastoris
Published in Preparative Biochemistry and Biotechnology, 2018
Rajkumar Paul, Selvarajan Karthik, Ponnusamy Vimalraj, Sankaranarayanan Meenakshisundaram, Perumal Kaliraj
LDP-TF and Ec-LDP-TF, tuftsin-based fusion proteins significantly enhanced the phagocytotic activity of macrophages and greatly suppressed the growth of human epidermoid carcinoma.[77] The T-peptide (TP), a novel tuftsin derivative made up of four tuftsin peptides efficiently extended the survival time of tumor-resected mice.[78] Tuftsin (Thr-Lys-Pro-Arg) covalently conjugated to fullerene C showed significant enhancement of phagocytosis, chemotaxis activities in another study.[79] The enhancement of mean peak titer by P-TUFT-ALT-2 suggesting its ability to stimulate B cells significantly by its immunomodulatory nature. Higher antibody titers could be correlated with the protective efficacy of the vaccine candidates as suggested by the previous studies where antibodies play a role in the clearance of L3 and microfilarial killing and also antibody-dependent cell-mediated cytotoxicity (ADCC) is believed to be one of the principle immunological mechanisms for clearing circulating parasites.[80] The result showed that there was a significant increase of proliferative response (9.46% higher) by P-TUFT-ALT-2 fusion protein than E-ALT-2. The epitopes were recognized by the memory T cells produced against the P-TUFT-ALT-2 antigen, indicating a strong cellular response elicited by the antigen.[81] Thus, the cost-effective large-scale production of P-TUFT-ALT-2 with enhanced immunogenicity would justify it as a potential vaccine candidate for human lymphatic filariasis.