• superfamily
  • The gene for LAG-3 lies adjacent to the gene for CD4 on human chromosome 12 (12p13) and is approximately 20% identical to the CD4 gene The LAG3 protein, which belongs to immunoglobulin (Ig) superfamily, comprises a 503-amino acid type I transmembrane protein with four extracellular Ig-like domains, designated D1 to D4. (wikipedia.org)
  • ligand
  • An initial characterization of the LAG-3 protein was reported in 1992 showing that it was a ligand for MHC class II antigens while a 1995 paper showed that it bound MHC Class II better than CD4. (wikipedia.org)
  • molecule
  • CD30 acts as a costimulatory molecule in thymic negative selection. (exbio.cz)
  • Recent clinical studies on several classes of experimental drugs, including small molecule inhibitors of protein kinases ( 14 - 16 ) and antibodies targeting vascular endothelial growth factor ( 17 ) or the RCC-associated antigen CAIX ( 18 ), have shown promise. (aacrjournals.org)
  • Evidence indicates that CD30 may act as a signal transduction molecule. (bio-rad-antibodies.com)
  • LAG3, which was discovered in 1990 and was designated CD223 (cluster of differentiation 223) after the Seventh Human Leucocyte Differentiation Antigen Workshop in 2000, is a cell surface molecule with diverse biologic effects on T cell function. (wikipedia.org)
  • Soluble
  • Soluble form of CD30 (sCD30) serves as a marker reflecting Th2 immune response. (exbio.cz)
  • Incubation of CD30 positive L540 cells with Ki-3 antibody weakly enhances release of soluble CD30 (in contrast to Ki-4, Ab00475). (absoluteantibody.com)
  • The phenotype of LAG-3 knockout mice, as established by the INSERM Strasbourg group in 1996, demonstrated that LAG-3 was vital for the proper functioning of natural killer cells but in 1998 Triebel, working with LAG-3 antibodies and soluble protein, found that LAG-3 did not define a specific mode of natural killing. (wikipedia.org)
  • Western Blot
  • Abgent's experienced staff custom validates more than 1,000 antibodies each month in Western Blot (WB), Immunofluorescence (IF), Immunohistochemistry (IHC), Flow Cytometry (FC) and additional applications. (abgent.com)
  • mAbs
  • CD30 has therefore attracted attention as a potential target for immunotherapy of HL and ALCL, and several mAbs specific for CD30 have been developed and tested in the clinic with varying degrees of success ( 6 - 10 ). (aacrjournals.org)
  • brentuximab vedotin
  • Upon binding to the target antigen, brentuximab vedotin is internalized and subsequently degraded within the lysosomal compartment. (haematologica.org)
  • Brentuximab vedotin includes an enzyme-sensitive cleavable linker that delivers the potent and highly toxic antimicrotubule agent monomethyl auristatin E or MMAE, a synthetic antineoplastic agent, to human specific CD30-positive malignant cells. (wikipedia.org)
  • The purpose of this study is to identify brentuximab vedotin drug-drug interactions in patients with CD30-positive cancers and to determine the main route of excretion. (clinicaltrials.gov)
  • protein
  • The present disclosure relates to anti-HCV core protein monoclonal antibodies, methods of making them, and their uses in the prevention, diagnosis, and/or treatment of disease including HCV infections. (patentsencyclopedia.com)
  • In developing antibody-drug conjugates, an anticancer drug (e.g. a cell toxin or cytotoxin) is coupled to an antibody that specifically targets a certain tumor marker (e.g. a protein that, ideally, is only to be found in or on tumor cells). (wikipedia.org)
  • The biochemical reaction between the antibody and the target protein (antigen) triggers a signal in the tumor cell, which then absorbs or internalizes the antibody together with the cytotoxin. (wikipedia.org)
  • However, the combination of MMAE linked to an anti-CD30 monoclonal antibody (cAC10, a cell membrane protein of the tumor necrosis factor or TNF receptor) proved to be stable in extracellular fluid, cleavable by cathepsin and safe for therapy. (wikipedia.org)
  • Ciechanover A (2006) Intracellular protein degradation: from a vague idea through the lysosome and the ubiquitin-proteasome system and onto human diseases and drug targeting. (springer.com)
  • potent
  • For example, an antimelanoma antibody with potent antitumor activity in a wild-type mouse model showed less efficacy in mice lacking activating FcγRI and FcγRIII ( 13 ). (aacrjournals.org)
  • Antibody-drug conjugates or ADCs are an important class of highly potent biopharmaceutical drugs designed as a targeted therapy for the treatment of people with cancer. (wikipedia.org)
  • Oflazoglu E, Stone IJ, Gordon K, Wood CG, Repasky EA, Grewal IS, Law CL, Gerber HP (2008) Potent anticarcinoma activity of the humanized anti-CD70 antibody h1F6 conjugated to the tubulin inhibitor auristatin via an uncleavable linker. (springer.com)
  • inhibit
  • LAG-3 may be a better checkpoint inhibitor target than CTLA-4 or PD-1 since antibodies to these two checkpoints only activate effector T cells, and do not inhibit Treg activity, whereas an antagonist LAG-3 antibody can both activate T effector cells (by downregulating the LAG-3 inhibiting signal into pre-activated LAG-3+ cells) and inhibit induced (i.e. antigen-specific) Treg suppressive activity. (wikipedia.org)
  • trastuzumab
  • Similar findings were made with clinically successful antibodies rituximab and trastuzumab, which had no detectable effect in mice lacking activating FcRs, but showed high levels of antitumor activity in mice deficient in inhibitory receptor FcγRIIB ( 14 ). (aacrjournals.org)
  • Trastuzumab emtansine, the other approved ADC, is a combination of the microtubule-formation inhibitor mertansine (DM-1), a derivative of the Maytansine, and antibody trastuzumab (Herceptin/ Genentech/Roche) attached by a stable, non-cleavable linker. (wikipedia.org)
  • targets
  • We provide tools for path-breaking research by developing antibodies that detect a comprehensive library of novel and established targets. (abgent.com)
  • For established targets we seek to add antibodies that recognize new epitopes, including post-translational modifications such as phosphorylation and methylation. (abgent.com)
  • For new targets we consult with leading experts to accelerate development of antibodies that will propel state-of-the-art research in cellular health and disease. (abgent.com)
  • therapeutic
  • Multiple approaches to enhance the efficacy of therapeutic antibodies, such as modification of glycosylation profiles, are currently being pursued by various biopharma companies. (aacrjournals.org)
  • More particularly, the present invention relates to nucleic acid molecules, including fusion constructs, having catalytic activity and the use of same in glycosylation engineering of host cells to generate polypeptides with improved therapeutic properties, including antibodies with increased Fc receptor binding and increased effector function. (freepatentsonline.com)
  • Therapeutic activity of humanized anti-CD20 monoclonal antibody and polymorphism in IgG Fc receptor FcγRIIIa gene," Blood 99:754-758, American Society of Hematology (Feb. 2002). (freepatentsonline.com)
  • expression
  • In T cells, CD30 expression is present on a subset of T cells that produce Th2-type cytokines and on CD4+/CD8+ thymocytes that co-express CD45RO and the IL4 receptor. (exbio.cz)
  • CD30 is expressed on activated lymphocytes, and binding by its ligands TRAF2 and TRAF5 results in the activation of NF-kappaB, thereby regulating gene expression. (absoluteantibody.com)
  • CHO-Anti-Human CD30 F(ab) stable cell line is clonally-derived from a CHO cell line, which has been transfected with an anti-human CD30 F(ab) gene to allow expression of the F(ab). (creativebiomart.net)
  • Pluckthun and Skerra, Expression of Functional Antibody Fv and Fab Fragments in Escherichia coli. (freepatentsonline.com)
  • In May 1996 scientists at the University of Florence showed that CD4+ T cells that were LAG-3+ preferentially expressed IFN-γ, and this was up-regulated by IL-12 while in 1997 the same group showed that IFN-γ production was a driver of LAG-3 expression during the lineage commitment of human naive T cells. (wikipedia.org)
  • The Triebel group in 1998 established that LAG-3 expression on activated human T cells is upregulated by IL-2, IL-7 and IL-12 and also showed that expression of LAG-3 may be controlled by some CD4 regulatory elements. (wikipedia.org)
  • refractory
  • On August 17, 2017 Inotuzumab ozogamicin was also approved by the US FDA for the treatment of adults with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL) A stable link between the antibody and cytotoxic (anti-cancer) agent is a crucial aspect of an ADC. (wikipedia.org)
  • therapeutics
  • Our findings provide evidence that CD70 is an attractive target for antibody-based therapeutics against metastatic RCC and suggest that anti-CD70 ADCs can provide a new treatment approach for advanced RCC patients who currently have no chemotherapeutic options. (aacrjournals.org)
  • immunotherapy
  • Entwicklung und Charakterisierung bispezifischer Antikörper-Derivate zur Immuntherapie CD19-positiver Leukämien und Lymphome" [Development and characterisation of bispecific antibody derivatives for the immunotherapy of CD19-positive leukaemia and lymphoma] (in German and English). (wikipedia.org)
  • biologically
  • Crown antibodies pass additional stringent quality requirements, including extended control sets, uniform results against multiple biologically relevant cell lines and tissues, and function in multiple applications. (abgent.com)
  • ADCs are complex molecules composed of an antibody linked to a biologically active cytotoxic (anticancer) payload or drug. (wikipedia.org)
  • contrast
  • This means that, in contrast to traditional chemotherapeutic agents, antibody-drug conjugates target and attack the cancer cell so that healthy cells are less severely affected. (wikipedia.org)
  • purification
  • Each antibody is crafted with care according to rigorous protocols for immunogen design and preparation, presentation to host animal, and high-affinity purification against the antigen. (abgent.com)
  • eosinophils
  • Importantly, only a few activated lymphocytes and eosinophils physiologically express this antigen and there is very little cross-reactivity with vital organs. (haematologica.org)
  • Cancer
  • By combining the unique targeting capabilities of monoclonal antibodies with the cancer-killing ability of cytotoxic drugs, antibody-drug conjugates allow sensitive discrimination between healthy and diseased tissue. (wikipedia.org)
  • Erickson HK, Park PU, Widdison WC, Kovtun YV, Garrett LM, Hoffman K, Lutz RJ, Goldmacher VS, Blattler WA (2006) Antibody-maytansinoid conjugates are activated in targeted cancer cells by lysosomal degradation and linker-dependent intracellular processing. (springer.com)
  • The second are antibodies to LAG3 which take the brakes off the anti-cancer immune response. (wikipedia.org)
  • cell
  • The CD30 antigen was subsequently also detected in mediastinal B-cell lymphoma, immunoblastic lymphoma, adult T-cell lymphoma and leukemias, mycosis fungoides, multiple myeloma, germinal center lymphoma, thyroid carcinoma and malignant mastocytosis. (haematologica.org)
  • Cytotoxic activity of these anti-CD70 ADCs was associated with their internalization and subcellular trafficking through the endosomal-lysosomal pathway, disruption of cellular microtubule network, and G 2 -M phase cell cycle arrest. (aacrjournals.org)
  • It is also expressed on a subset of activated human T-cells, and by a few extrafollicular T and B-cell blasts in normal lymph nodes. (bio-rad-antibodies.com)
  • Restoration of Viral Immunity in Immunodeficient Humans by the Adoptive Transfer of T Cell Clones. (freepatentsonline.com)
  • Human T Regulatory Cell Therapy: Take a Billion or So and Call Me in the Morning. (freepatentsonline.com)
  • efficacy
  • The low doses of antibody required for ADCC activity irrespective of donor genotype, the ability to mediate ADCC in target cells expressing low levels of CD30, and increased in vivo efficacy support the development of MDX-1401 for treatment of malignant lymphoma. (aacrjournals.org)
  • ADCs
  • For a video on the principles of ADCs see Nature Biotechnology Animation Antibody-drug conjugates. (wikipedia.org)
  • In this chapter, we review various linkers, cleavable and non-cleavable, that have been reported, main approaches that have been used to attach the linkers to the antibodies, and the impact of various linkers on the properties of the resulting ADCs, such as their cytotoxic and antitumor activities, stabilities in circulation and tissues, and the extent of killing of bystander cells and of multidrug-resistant cells. (springer.com)