China
Africa
Explore chapters and articles related to this topic
Preformulation of New Biological Entities
Published in Sandeep Nema, John D. Ludwig, Parenteral Medications, 2019
Riccardo Torosantucci, Vasco Filipe, Jonathan Kingsbury, Atul Saluja, Yatin Gokarn
Multispecific antibodies are engineered to combine two or more specific antigen-binding elements within a single molecule. This allows targeting of multiple epitopes simultaneously, thus providing the ability to cross-link the targets (such as the therapeutic target and an effector site) or to bind multiple components of a single target (providing higher specificity than binding to a single component of the target). The generation of multispecific antibodies has a long history, probably beginning in the early 1960s [39], but only gaining biotherapeutic interest in the 1980s with the advent of quadroma technology [40]. Since then, several different engineering strategies and formats have been developed to overcome the limitations of the early examples. The heterodimeric bispecific antibody approach, pioneered by Genentech, combines heavy chain/light chain pairs from two different antibodies [41] and results in a bispecific/monovalent binding arrangement. To maintain multivalent binding, Abbvie and Sanofi developed the dual variable domain immunoglobulin and crossover dual-variable (CODV) immunoglobulin-like protein formats, respectively [42,43]. These formats both involve fusing additional variable domains onto monoclonal heavy chain/light chain pairs. Two multispecific antibodies have gained regulatory approval: catumaxomab (Removab®), a heterodimeric bispecific antibody targeting CD3 and epithelial cell adhesion molecule (EpCAM), and blinatumomab (Blincyto®), a bispecific tandem of single-chain variable domains directed against CD3 and CD19. In addition, several more are in clinical trial including a trispecific modality for treating human immunodeficiency virus (HIV) infection. This incorporates three broadly-neutralizing anti-HIV envelope protein functions onto the CODV scaffold [44; ClinicalTrials.gov Identifier: NCT03705169].
A comparative study of the bispecific monoclonal antibody, blinatumomab expression in CHO cells and E. coli
Published in Preparative Biochemistry and Biotechnology, 2018
Fatemeh Naddafi, Farshad H. Shirazi, Yeganeh Talebkhan, Maryam Tabarzad, Farzaneh Barkhordari, Zahra Aliabadi Farahani, Elham Bayat, Reza Moazzami, Fereidoun Mahboudi, Fatemeh Davami
The CD19/CD3-bispecific T cell-engaging (BiTE®) monoclonal antibody, blinatumomab sequence was successfully cloned into the NcoI/HindIII site of the pET-22b vector (for expression in E. coli). The restriction enzyme analysis using HindIII and NcoI enzymes showed two fragments with expected sizes at 5500 and 1600 bp (Figure 2). Moreover, this antibody was successfully cloned into the EcoRV site of the FC550A-1 vector (for expression in CHO). The restriction enzyme analysis using XhoI enzyme showed two fragments with expected sizes at 4500 and 3000 bp (Figure 3). This antibody was also successfully cloned into the NheI/HindIII site of pcDNA3.1 (+) vector (for expression in CHO). The restriction enzyme analysis using NheI and HindIII restriction enzymes showed two fragments with expected sizes at 5400 and 1600 bp (Figure 4).