2013
DOI: 10.4161/mabs.23043
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Monoclonal antibody therapeutics with up to five specificities: Functional enhancement through fusion of target-specific peptides

Abstract: The recognition that few human diseases are thoroughly addressed by mono-specific, monoclonal antibodies (mAbs) continues to drive the development of antibody therapeutics with additional specificities and enhanced activity. Historically, efforts to engineer additional antigen recognition into molecules have relied predominantly on the reformatting of immunoglobulin domains. In this report we describe a series of fully functional mAbs to which additional specificities have been imparted through the recombinant… Show more

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Cited by 46 publications
(33 citation statements)
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“…The central barrier is to develop next generation targeting ligands with multispecificity that can be tuned and applied to different cancer types [10,11]. While it is a great achievement to engineer a monoclonal antibody to acquire multispecificity, the process is often limited [12], in addition to high manufacturing cost. In this study, we aimed to develop a targeting ligand with tetraspecificity capable of binding four cell surface biomarkers, namely, VEGFR2, α v β 3 integrin, EGFR, and HER2, which are of significant cancer targeting interest [13–16].…”
Section: Introductionmentioning
confidence: 99%
“…The central barrier is to develop next generation targeting ligands with multispecificity that can be tuned and applied to different cancer types [10,11]. While it is a great achievement to engineer a monoclonal antibody to acquire multispecificity, the process is often limited [12], in addition to high manufacturing cost. In this study, we aimed to develop a targeting ligand with tetraspecificity capable of binding four cell surface biomarkers, namely, VEGFR2, α v β 3 integrin, EGFR, and HER2, which are of significant cancer targeting interest [13–16].…”
Section: Introductionmentioning
confidence: 99%
“…Moreover, all of these formats rely on the display of Fvs, which often exhibit poor stability and promote aggregation of the composite molecule 24,56 . Hence, other antibody formats that employ alternative binding moieties have been developed, such as Zybodies 57 and Fynomabs 7 . Variable-domain-only multispecifics with >2 specificities, such as the triplebody, have only been described in single-chain formats and only up to 3 specificities.…”
Section: Discussionmentioning
confidence: 99%
“…To address this challenge, modified antibody formats (e.g., knobs into holes [40], IgG-scFv [41], and DVD-Ig [21]) have been created using protein engineering methods. Often these approaches suffer from protein instability and low expression yields, although the recently described peptide fusion approach overcomes many of these problems (42). The approach used here involves chemical conjugation of a peptide or small molecule to a monoclonal antibody that possesses a desired specificity.…”
Section: Discussionmentioning
confidence: 99%