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BsAb Application in Radioimmunotherapy

Creative Biolabs is experienced in engineering and producing payload delivery bispecific antibodies (BsAbs) products with experimentally verified high-affinity. With experienced experts hammering at Creative Biolabs, we are confident in offering first class BsAbs to meet your project development.

In cancer therapy, radioimmunotherapy refers to the therapy in which an antibody that targets tumor-associated antigen is used to deliver cytotoxic radiation to tumor cells. BsAbs are capable of binding two or more antigens/receptors at the same time or bringing two different targets together. This character makes BsAbs widely used in the payload (drugs, radiolabels or other small molecules) delivery. BsAb-mediated payload delivery is highly specific and sensitive for targets during delivery and is rapidly developed for pretargeting method in radioimmunodetection and radioimmunotherapy.

Pretargeting Method for Radioimmunotherapy

Though malfunctioning and uncontrolled, tumor cells are still “self” cells. How to target tumor cells over the surrounding tissues is the main obstacle for radioimmunodetection and radioimmunotherapy. High selectivity and specificity guarantee high image resolution in radioimmunodetection, and better efficacy and low toxicity in radioimmunotherapy. Previously, radioactive monoclonal antibodies or antibody fused with radioactive materials were used for such purposes. However, disadvantages of these drugs such as low stability, high immunogenicity, and low affinity for tumor cells limited the efficacy. The long-time and high-dose exposure of normal cells to radiation also leads to high toxicity. An alternative way is the pretargeting method, which separates the localization of tumor (by specific antibody) from the subsequent delivery of the radionuclide. In this method, radiation is not applied until excess free antibodies being cleared from the body.

Schematic diagram of the principal methods for radioimmunotherapy with BsAb pretargeted RIT. (Goldenberg, D. M. 2009)

Figure 1. Schematic diagram of the principal methods for radioimmunotherapy with BsAb pretargeted RIT. (Goldenberg, D. M. 2009)

Examples of BsAb

BsAbs can bind two/multiple targets sequentially and can be entirely humanized to decrease immunogenicity, thus are great therapeutic reagents in pretargeting settings. Dock-and-lock (DNL) BsAb is one type of BsAbs that is already applied to radioimmunodetection/ radioimmunology. DNL BsAb TF2 (from Immunomedics) can simultaneously bind two CEA (on tumor surface) and one hapten, a peptide which can be labeled with radioactive molecules. In a pretargeting setting, cold TF2 is first injected for tumor binding. Some time is allowed for the clearance of unbound TF2 from organs and the blood system. Then a Lutetium-177-labeled or Indium-111-labeled payload is injected for imaging. TF2 can also target GaHSG and CEA, which function is useful for immuno-positron emission tomography. DNL BsAb lacks the Fc region of IgG and has rather short serum half-life, which is an advantage for radioimmunotherapy and radioimmunodetection. It ensures rapid clearance from the body (even kidneys and liver) and lower toxicity. Pretargeting with DNL BsAbs improves the tumor/blood ratio of payloads.

Schematic diagram of the Dock-and-Lock modules and how they are assembled to generate BsAb.

Figure 2. Schematic diagram of the Dock-and-Lock modules and how they are assembled to generate BsAb.

As an international company, Creative Biolabs is proud to present our integrated and advanced engineering platforms, which ensure budget and time-saving BsAb services for all customers. Our talented and well-trained scientists are here to support your research in academia and pharmaceutics.

Recommended products: Dock and lock bispecific antibody (DNL BsAb).

References

1. Goldenberg, D. M. Some like it hot: lymphoma radioimmunotherapy. Blood. 2009, 113(20): 4823-4824.
2. van de Watering, F. C.; et al. Pretargeted imaging and radioimmunotherapy of cancer using antibodies and bioorthogonal chemistry. Frontiers in medicine. 2014, 1: 44.
3. Sharkey, R. M.; et al. Recombinant bispecific monoclonal antibodies prepared by the dock-and-lock strategy for pretargeted radioimmunotherapy. In Seminars in nuclear medicine. 2010, 40(3): 190-203.

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