Bispecific antibodies: a mechanistic review of the pipeline

AF Labrijn, ML Janmaat, JM Reichert… - Nature reviews Drug …, 2019 - nature.com
AF Labrijn, ML Janmaat, JM Reichert, PWHI Parren
Nature reviews Drug discovery, 2019nature.com
The term bispecific antibody (bsAb) is used to describe a large family of molecules designed
to recognize two different epitopes or antigens. BsAbs come in many formats, ranging from
relatively small proteins, merely consisting of two linked antigen-binding fragments, to large
immunoglobulin G (IgG)-like molecules with additional domains attached. An attractive bsAb
feature is their potential for novel functionalities—that is, activities that do not exist in
mixtures of the parental or reference antibodies. In these so-called obligate bsAbs, the …
Abstract
The term bispecific antibody (bsAb) is used to describe a large family of molecules designed to recognize two different epitopes or antigens. BsAbs come in many formats, ranging from relatively small proteins, merely consisting of two linked antigen-binding fragments, to large immunoglobulin G (IgG)-like molecules with additional domains attached. An attractive bsAb feature is their potential for novel functionalities — that is, activities that do not exist in mixtures of the parental or reference antibodies. In these so-called obligate bsAbs, the physical linkage of the two binding specificities creates a dependency that can be temporal, with binding events occurring sequentially, or spatial, with binding events occurring simultaneously, such as in linking an effector to a target cell. To date, more than 20 different commercialized technology platforms are available for bsAb creation and development, 2 bsAbs are marketed and over 85 are in clinical development. Here, we review the current bsAb landscape from a mechanistic perspective, including a comprehensive overview of the pipeline.
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