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Bispecific Antibody -Toxin Fusion Protein Generation Service

Based on the advanced bispecific antibodies (BsAbs) platform we have established, Creative Biolabs is proud to offer high affinity bispecific antibody-toxin fusion proteins for both academic and industrial purposes.

Targeted toxins (TTs) are a set of therapeutic molecules which directed against human cancer. TTs are able to be developed to be selective against a number of cancer types, through directing TTs toward cancer specific targets using tumor reactive ligands. Due to the designed purpose of specifically break cancerous cells without damaging healthy cells, their potential outweighs a majority of the non-specific therapies, including radiotherapy and chemotherapy currently used in cancer patients. In recent years, the potential of TTs has increased in the field of cancer research by continuous advance using genetic engineering. Most TTs attack cancer through a single targeting molecule. However, various novel bispecific ligand-directed toxins (BLTs) are also developed to simultaneously target both solid tumors and their associated neovasculature.

Tandem scFv-toxin

In BsAb-toxin fusion proteins, tandem scFv-toxin is a representative and most widely used. Tandem scFv-toxin, also known as bispecific ligand-directed toxin (BLT), is synthesized by fusing a truncated toxin with two well-established ligands. According to the strategy of immunotherapy, BLTs can show better activities than their monospecific counterparts because the two ligands can bind to their own specific receptors on the same cells simultaneously with increased total targeting capability, therefore the toxin portion can bind and kill target cells more effectively. Meanwhile, the catalytic toxins, such as pseudomonas exotoxin (PE) and diphtheria toxin (DT), are chosen because they can enter cytosol and induce cell death. DTEGFATF is a BLT comprising diphtheria toxin (DT), and EGFATFKDEL is a BLT comprising pseudomonas exotoxin (PE). Both of the two BLTs target two receptors, urokinase plasminogen activator receptor (uPAR) and epidermal growth factor receptor (EGFR), which are generally overexpressed on the cell surface of a number of different cancers. Because urokinase-type plasminogen activator receptor (uPAR) is overexpressed not only on solid tumors, but also on the neovasculature, uPAR-targeting was also used by these two BLTs.

Schematic diagram of tandem scFv-toxin.

Figure 1. Schematic diagram of tandem scFv-toxin.

Examples of Tandem scFv-toxin

Except for the two BLTs mentioned above, several other BLTs have been designed. For example, a novel BLT is developed, in which both human EGF and IL-4 cytokines are introduced onto the same single chain molecule with deimmunized pseudomonas exotoxin (dEGF4KDEL). Besides, the crucial amino acids dictating B cell formation of neutralizing anti-toxin antibodies were mutated. It has demonstrated that dEGF4KDEL was extremely effective following systemic injection against established orthotopic MIA PaCa-2 pancreatic cancer and selectively prevented metastasis.

Targeted toxins can be an alternative therapy in antitumor treatment. Creative Biolabs is professional in generating bispecific antibody-toxin fusion proteins with increased targeting capability and reduced immunogenicity, which can meet your specific requirements in scientific and clinical researches.

References

1. Vallera, D. A.; et al. Genetic alteration of a bispecific ligand-directed toxin targeting human CD19 and CD22 receptors resulting in improved efficacy against systemic B cell malignancy. Leukemia research. 2009, 33(9): 1233-1242.
2. Oh, S.; et al. A deimmunized bispecific ligand directed toxin that shows an impressive anti-pancreatic cancer effect in a systemic nude mouse orthotopic model. Pancreas. 2012, 41(5): 789-96.

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