China
Africa
Explore chapters and articles related to this topic
Transplantation immunology
Published in Gabriel Virella, Medical Immunology, 2019
Satish N. Nadig, Jane C. Kilkenny
Anti-T-cell monoclonal antibodies obtained from mice and directed against human T cells, particularly those reacting with the CD3 marker (muromonab CD3, OKT3), have been extensively used in the management of transplanted patients. Their mechanisms of action are multiple. CD3 monoclonal antibodies cause depletion of CD3+ T lymphocytes, and it is likely that the depletion is due to complement-mediated lysis, opsonization, and ADCC. CD3 monoclonal antibodies also cause downmodulation of CD3 on the cell surface of otherwise viable T cells and may induce T-cell anergy.
Affinity-controlled capture and release of engineered monoclonal antibodies by macroporous dextran hydrogels using coiled-coil interactions
Published in mAbs, 2023
Seyed Farzad Baniahmad, Romane Oliverio, Ines Obregon-Gomez, Alma Robert, Anne E.G. Lenferink, Elena Pazos, Nick Virgilio, Xavier Banquy, Gregory De Crescenzo, Yves Durocher
Monoclonal antibodies (mAbs) are one of the most successful tools available for cancer therapy. Currently, more than 100 antibodies have been approved by the US Food and Drug Administration. Since the approval of muromonab-CD3 (Orthoclone; Ortho Biotech) in 1986 as the first therapeutic mAb for use in humans, these proteins have been applied to the treatment of oncological, immunological, and infectious diseases.1–3 Parenteral injections are the preferred route of administration for most antibodies. Among all, the intravenous injection is superior in terms of pharmacokinetic and pharmacodynamic efficacy of drug delivery to the body, and is comparatively less immunogenic.4 However, to obtain restorative benefits and therapeutic advantages and compensate for the dose-dependent elimination, antibodies must be delivered either in large doses or by multiple injections at short intervals. For instance, trastuzumab (TZM) which is used in the adjunctive treatment of human epidermal growth factor receptor (HER2)-overexpressing breast cancer can be administered in some cases up to 3 times a week over a year.5 In addition to the high cost of such treatment, this may result in side effects and negative health outcomes, and compromise patient compliance.5–7
International nonproprietary names for monoclonal antibodies: an evolving nomenclature system
Published in mAbs, 2022
Sofia S. Guimaraes Koch, Robin Thorpe, Nana Kawasaki, Marie-Paule Lefranc, Sarel Malan, Andrew C.R. Martin, Gilles Mignot, Andreas Plückthun, Menico Rizzi, Stephanie Shubat, Karin Weisser, Raffaella Balocco
Following the approval of Orthoclone OKT3, the INN Programme received an INN request for this substance in 1987 with the requested INN “muromonab-CD3”; this reflected the facts that the monoclonal antibody targets the CD3 complex and the name is an abbreviation of ‘murine monoclonal antibody’. At this time, the name muromonab-CD3 was already being widely used ‘unofficially’ in the medical and scientific literature prior to its submission to the INN program. Owing to this and despite the fact that numbers and hyphenated constructs are to be avoided according to the INN General principles for guidance in devising INN for pharmaceutical substances,9 the INN Expert Group confirmed muromonab-CD3 as the INN for this substance.10 However, it was made clear that this decision would not be considered a precedent for naming future monoclonal antibodies and no further products were named similarly. The reasoning in the INN General Principles for Guidance in devising INN for pharmaceutical substances for avoiding numbers, hyphens, and such is that when used in a medical prescription, or when spoken, they can be easily confused with the dose or frequency of use.9,11
Broad reactivity and enhanced potency of recombinant anti-EGFR × anti-CD3 bispecific antibody-armed activated T cells against solid tumours
Published in Annals of Medicine, 2022
Manley T. F. Huang, Vikram Sharma, Andrew Mendelsohn, Qisheng Wei, Jinjing Li, Bo Yu, James W. Larrick, Lawrence G. Lum
The variable light and heavy gene sequences from the DrugBank amino acid entry for Erbitux were back-translated using the most common homologous mouse sequences in the IMGT database. The variable light and heavy chain genes for humanized muromonab-CD3 were designed based on amino acid sequences in US patent 5,885,573. The OKT3 scFv-Erbitux-heavy chain fusion gene was assembled in the order: variable light chain – (G4S)6 linker-variable heavy chain – (G4S)5 (with a change in repeat 3 to introduce a G to T substitution) linker – Erbitux heavy chain variable sequence - human IgG1 Fc. Coding regions for the Erbitux light and OKT3scFv-Erbitux fusion genes were then subcloned into the proprietary expression vector SwiMR (US9910038B2) which contains selectable markers for puromycin or neomycin. The amino acid sequences for the Erbitux light chain and humanized OKT3-Erbitux heavy chain fusion chain expression cassettes are shown in Figure 4.