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Tetravalent Bispecific T Cell Engaging Antibody Design and Construction Service

All products and services are For Research Use Only and CANNOT be used in the treatment or diagnosis of disease.

The most promising strategy in cancer treatment is to direct cytotoxic T cells to kill tumor cells. The clinical success of CAR-T therapy also highlights the value of using cytotoxic T cells (CTL) to treat cancer. This can be achieved using dual targeting antibodies that simultaneously bind to tumor-specific antigens on tumor cells and CD3 on T cells, bringing these cells in close proximity and causing the T cells to kill tumor cells. Most bispecific antibodies are constructed as heterodimers, which have monovalent binding to antigens highly expressed on tumor cells and CD3 on T cells.

At Creative Biolabs, we have developed a novel tetravalent bispecific (TetraBi) platform: a tumor-associated antigen specific, T-cell engaging antibody that provides significant advantages over traditional BiTEs. Compared with the traditional bispecific antibody, the TetraBi format offers several significant advantages over other bispecific antibody formats and other approaches to T cell-based therapy.

Design and Construction of TetraBi Antibody

We provide the generation and characterization services of tetravalent, bispecific antibody derivatives to enhance the anti-tumor activity mediated by T cell engager. Their bispecific molecules are composed of an IgG antibody, designated the master or parent module, with scFvs of different specificities coupled to the C terminus of the heavy chain. The bispecific molecule contains flexible peptide sequences between the VH and VL domains and between the parent IgG and other scFv moieties to form scFv. We chose to apply the well-known sequence motif (G4S) to these two connections. In contrast to monospecific antibodies, this novel form of TetraBi antibody can simultaneously involve different target antigens in a bivalent and monovalent manner in the tumor microenvironment and has potential therapeutic significance. In addition, it provides a greater therapeutic index compared to the more traditional bispecific form characterized by monovalent recognition of tumor antigens.

Schematic diagram of tetravalent bispecific antibody.

Fig.1 Schematic diagram of tetravalent bispecific antibody.

Advantages of TetraBi Antibody

  • Enhanced potency through bivalent binding to tumor cells. By including two tumor antigen binding sites, our antibodies are designed to form a stronger connection with tumor cells than molecules with only a single binding site.
  • Enhance safety through functional unit price binding to CD3. By placing the CD3 binding domain in the hinge region of the molecule, our antibodies behave as if they have a single binding site for CD3. This is important to prevent TetraBi antibodies from activating T cells in the absence of tumor cells, as this can lead to harmful toxicity, such as cytokine release syndrome.
  • A better dosage can be achieved by including the Fc region. By including the Fc region, our TetraBi antibody is designed to have a long circulating half-life, thus providing patients with a more convenient dosage.
  • Control immune effector functions through Fc engineering. By introducing defined mutations into the Fc region, our TetraBi antibody is designed to reduce or eliminate Fc-mediated interactions that can cause undesirable side effects, such as cytokine release syndrome.
  • Low immunogenicity. By closely resembling natural human antibodies, our TetraBi antibody has a reduced risk of immunogenicity, which may otherwise lead to reduced efficacy.
  • Simplify manufacturing. By constructing a symmetrical molecule with two identical heavy chains and two identical light chains, our molecule can eliminate the complexity caused by potential chain mismatches.

For more detailed information, please feel free to contact us or directly sent us an inquiry.

References

  1. Wu, S. C., et al. (2016). Bispecific antibody conjugated manganese-based magnetic engineered iron oxide for imaging of HER2/neu-and EGFR-expressing tumors. Theranostics, 6(1), 118.
  2. Schanzer, J., et al. (2011). Development of tetravalent, bispecific CCR5 antibodies with antiviral activity against CCR5 monoclonal antibody-resistant HIV-1 strains. Antimicrobial agents and chemotherapy, 55(5), 2369-2378.
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