Bispecific Antibody (BsAb) Design Service for Signaling Interference

As a leading developer and manufacturer of antibodies, Creative Biolabs takes pride in offering high-affinity bispecific antibodies (BsAb) for both academic and industrial applications. Leveraging our robust BsAb production platform and a team of experienced scientists, we provide a diverse range of BsAbs designed for signaling interference. These include various formats and BsAbs targeting multiple signaling pathways, empowering you to optimize your research and therapeutic strategies.

Introduction

BsAbs are engineered molecules designed to simultaneously target two distinct antigens or receptors, often from different signaling pathways. By binding to two different targets at once, either ligands or receptors, BsAbs can interfere with signal transduction by blocking unnecessary or harmful pathways. This dual-target approach allows for more precise modulation of cellular signaling, potentially enhancing therapeutic efficacy in treating diseases like cancer or autoimmune disorders, enhancing therapeutic efficacy and minimizing resistance.

Fig.1 Dual signaling inhibition targets two different receptors.¹

Mechanism of BsAbs for Signaling Interference

BsAbs interfere with signaling by targeting two distinct antigens or different regions of a single antigen. There are multiple ways in which BsAbs can target two pathways. Primarily, BsAbs block receptor-ligand interactions, disrupting downstream signaling. They can also induce receptor internalization, preventing receptor crosslinking (homodimerization and/or heterodimerization) and subsequently suppressing downstream effects, such as angiogenesis suppression and cell proliferation inhibition. Additionally, IgG-based BsAbs, featuring an Fc region, facilitate antibody-dependent cellular phagocytosis (ADCP) and antibody-dependent cellular cytotoxicity (ADCC), ultimately triggering apoptosis.

Multiple Pathways Blockade by BsAbs

BsAbs can simultaneously block multiple signaling pathways, enhancing therapeutic efficacy. By targeting receptor tyrosine kinases (RTKs), BsAbs can disrupt signaling that promotes tumor cell growth and survival. They also block cytokines and angiogenic factors, which are involved in inflammation and tumor blood vessel formation. BsAbs can interfere with oncogenic signaling pathways, such as PI3K/AKT/mTOR and MAPK/ERK, which are commonly activated in cancers. BsAbs targeting PD-1/PD-L1 simultaneously and other immune checkpoints can enhance T-cell antitumor activity by blocking multiple coinhibitory receptors and modifying the immunosuppressive tumor microenvironment. BsAbs simultaneously blocking CD47/SIRPα and PD-1/PD-L1 enhance T-cell cytotoxicity and macrophage phagocytosis. This multi-target approach not only helps overcome resistance to therapies like tyrosine kinase inhibitors (TKIs) but also improves treatment outcomes by addressing the complexity of cancer biology and immune evasion.

Fig.2 Schematic overview of a BsAb in cancer.^2,4

BsAbs Formats for Signaling Pathway Blockade

Various BsAb formats have been developed to block signaling pathways by targeting receptors or their ligands on cell surfaces. Examples include DVD-Igs, which target receptor ligands such as TNF+IL-17 or IL1α+IL1β, disrupting inflammatory signaling. Dual-action Fab (DAF)-IgG formats can target receptor pairs like HER1+HER3 to inhibit oncogenic signaling. (scFv)₂-HSA and tetravalent-IgG derivatives (Tv-IgGs) are designed to target combinations like Her2+Her3 or IGF1R+Her3, blocking growth factor pathways that promote cancer progression. CrossMabs, targeting receptor ligands such as VEGFA and angiopoietin 2, can block angiogenesis and tumor blood vessel formation. These BsAb formats offer versatile strategies for modulating multiple signaling pathways.

Published Data

1. BsAb for Cell-Type Specific Wnt Signaling Interference

Researchers developed a novel method for cell type-selective signaling blockade using the Wnt/β-catenin pathway as a model. They constructed a BsAb against the Wnt co-receptor effector antigen LRP6 alongside a cell type-specific guide antigen. This approach enhanced signaling inhibition potency over 100-fold in a cell type-selective manner, dependent on the guide antigen's expression and the anti-guide antibody's affinity. Both internalizing and non-internalizing guide antigens were effective, with internalizing BsAbs blocking signaling from all ligands by removing the receptor from the cell surface.

Fig.3 The construction and anti-Wnt signaling activity of guided anti-LRP6 bsAbs.^3,4

Creative Biolabs has been dedicated to BsAb research for many years. In addition to offering high-quality dual signaling pathway blocking BsAb products, we also provide customized BsAb development services to meet your specific needs and accelerate your project.