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CREATIVE BIOLABS • RECOMBINANT ANTIBODY
45-1 Ramsey Road, Shirley, NY 11967, USA
Email: info@creative-biolabs.com
6 / 20
mAb-mediated cell signaling. In the absence of immune effector mechanisms, some mAbs can induce
the death of malignant cells in vitro, and presumably in vivo. The MoA of inducing death within the target
cell plays a role via signaling mediated by mAb which can promote receptor activation or block receptor-
ligand interactions. Receptor signaling for many receptors is promoted by ligand-induced dimerization
that can often be mimicked, at least in part, with a bivalent IgG antibody or secondary crosslinking.
Another receptors require higher-order crosslinking (clustering), not just dimerization, to trigger their
activation. For example, at least five different engineered versions of FGF21 with improved properties
have progressed to early clinical development, including LY2405319 and PF-05231023, which have
shown preliminary evidence for clinical benefit in patients with obesity and type 2 diabetes. The well-
characterized of this class antibody as agonist are members of the TNF receptor superfamily (TNFRSF),
which are of high interest as therapeutic targets owing to their roles in apoptosis and T cell activation.
In some vital signaling pathway which accompanied by the disease occurred, antibody can down regulate
receptor by enhanced internalization and degradation. A synergistic down regulation of receptor
tyrosine kinases by combining Ab - binding nonoverlapping epitopes leading to a more efficient shutoff
of EGFR signaling was observed for both anti‐EGFR and HER2.
Even when a mAb is known to alter signaling properties and is effective clinically, it is difficult to
determine whether the therapeutic effect of the mAb results from the mAb interrupting the interaction
between an activating ligand and the receptor, from inhibiting the dimerization or clustering of the
receptor, or from having a direct effect on receptor signaling. Individual receptors in one family can have
multiple ligands, mAbs can alter dimerization properties and a mAb can have different signaling
properties depending on whether it is targeting a homodimeric or a heterodimeric receptor, such as
ERBB tyrosine kinase family. In the development and clinical testing of novel therapeutics, especially
therapeutic antibodies, understanding this complexity of mAb – mediated cell signaling in target cell
should not be ignored.
ADCC (Antibody-dependent cell-mediated
cytotoxicity). mAbs can induce ADCC by binding to
FcRs, which are expressed by a variety of immune
effector cells, including natural killer (NK) cells,
granulocytes, monocytes and macrophages. To
trigger ADCC, the variable region of an antibody
binds to a specific antigen expressed on the
surface of a target cell. The antibody’s Fc region
can bind to Fc receptors (FcRs) expressed on
leukocyte, and then be able to recruit immune-
effector cells (such as macrophages and NK cells)
that express various receptors able to bind to the
Fc, and thus activate

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Bispecific Antibody Production

  • 1. CREATIVE BIOLABS • RECOMBINANT ANTIBODY 45-1 Ramsey Road, Shirley, NY 11967, USA Email: info@creative-biolabs.com 6 / 20 mAb-mediated cell signaling. In the absence of immune effector mechanisms, some mAbs can induce the death of malignant cells in vitro, and presumably in vivo. The MoA of inducing death within the target cell plays a role via signaling mediated by mAb which can promote receptor activation or block receptor- ligand interactions. Receptor signaling for many receptors is promoted by ligand-induced dimerization that can often be mimicked, at least in part, with a bivalent IgG antibody or secondary crosslinking. Another receptors require higher-order crosslinking (clustering), not just dimerization, to trigger their activation. For example, at least five different engineered versions of FGF21 with improved properties have progressed to early clinical development, including LY2405319 and PF-05231023, which have shown preliminary evidence for clinical benefit in patients with obesity and type 2 diabetes. The well- characterized of this class antibody as agonist are members of the TNF receptor superfamily (TNFRSF), which are of high interest as therapeutic targets owing to their roles in apoptosis and T cell activation. In some vital signaling pathway which accompanied by the disease occurred, antibody can down regulate receptor by enhanced internalization and degradation. A synergistic down regulation of receptor tyrosine kinases by combining Ab - binding nonoverlapping epitopes leading to a more efficient shutoff of EGFR signaling was observed for both anti‐EGFR and HER2. Even when a mAb is known to alter signaling properties and is effective clinically, it is difficult to determine whether the therapeutic effect of the mAb results from the mAb interrupting the interaction between an activating ligand and the receptor, from inhibiting the dimerization or clustering of the receptor, or from having a direct effect on receptor signaling. Individual receptors in one family can have multiple ligands, mAbs can alter dimerization properties and a mAb can have different signaling properties depending on whether it is targeting a homodimeric or a heterodimeric receptor, such as ERBB tyrosine kinase family. In the development and clinical testing of novel therapeutics, especially therapeutic antibodies, understanding this complexity of mAb – mediated cell signaling in target cell should not be ignored. ADCC (Antibody-dependent cell-mediated cytotoxicity). mAbs can induce ADCC by binding to FcRs, which are expressed by a variety of immune effector cells, including natural killer (NK) cells, granulocytes, monocytes and macrophages. To trigger ADCC, the variable region of an antibody binds to a specific antigen expressed on the surface of a target cell. The antibody’s Fc region can bind to Fc receptors (FcRs) expressed on leukocyte, and then be able to recruit immune- effector cells (such as macrophages and NK cells) that express various receptors able to bind to the Fc, and thus activate