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The Promise of Engineered Bispecific Antibodies in Cancer Treatment

Bispecific antibodies (bsAbs) are antibodies containing two antigen-binding sites for different epitopes (usually on two separate antigens). Due to the unique mechanism of action, bispecific antibodies attract continuous interests of researchers for therapeutic use, many of which are under clinical trials.

Bispecific antibody applications cover oncology, immunology, hematology, ophthalmology, osteology, pulmonary and respiratory diseases, pretargeting systems, diagnostics, gene therapy, etc. Most of them have received obvious improvement and appear to be promising in future therapeutic applications, especially in cancers.

Three recent studies in ScienceScience Translational Medicine, and Science Immunology respectively demonstrate the efficacy of newly engineered bispecific antibodies against previously inaccessible tumor cell targets for the first time. Researchers engineered bispecific antibodies, in which one site tightly bound to the mutant p53 antigen on tumor cells and the other recruited a T cell to destroy the peptide-presenting cell. In the mouse models, the engineered antibodies were able to specifically kill cancerous cells, both in solid tumors and in T cell leukemia, without harming healthy cells.

Researchers illustrate that the technology of bispecific antibodies is not new, as the FDA has approved the first bispecific antibody as early as 2015. But using these bispecific antibody fragments with high affinity does provide a highly sensitive means of detecting a peptide presented by the major histocompatibility complex in a tiny amount, which is promising in cancer immunotherapy.

However, it may take more few years to translate these preclinical findings into clinical trials along with the optimization of bispecific antibodies. Assistance and consultancy from biotechnology industrial companies are required to facilitate cancer-related technology.

Creative Biolabs is a well-established life science company dedicated to antibody development and manufacturing for years. It provides bispecific antibodies for signaling pathway interference, payload delivery, and immune cell recruitment, in the application of oncology. Moreover, it has involved bispecific antibody engineering, design, etc. in different application fields.

Application in Immunology

BsAbs are used to interfere with signaling receptors in immunological disorders of chronic inflammation, autoimmune disease, hypersensitivity, immune deficiency, transplant rejection, etc.

Application in Hematology

Currently, BsAb drugs are developed for blood disease treatment based on two major mechanisms, T cell recruitment and forced protein association. They have been applied to treat blood cancers such as acute myeloid leukemia (AML), chronic lymphocytic leukemia (CLL), and hemophilia.

Application in Osteology

Tumors developed in bones are a result of malfunctioning crosstalk between osteoclasts and osteoblasts, which will disrupt the balance of bone formation and resorption in bone remodeling. BsAbs are potential to be the next generation therapeutics for Osteology with the development of nanobody BsAb, ALX-0141.

Application in Radioimmunotherapy

In radioimmunotherapy, an antibody that targets tumor-associated antigen is used to deliver cytotoxic radiation to tumor cells. BsAbs are widely used to deliver the payloads like drugs and radiolabels due to the feature of simultaneously binding two or more antigens/receptors, which is highly specific and sensitive.

Taking advantage of a patient’s own immune system to fight cancer has long been an objective of researchers and physicians. Based on the unifying principle of adapting immune therapies with greater precision while going after targets that are traditionally considered to be untargetable, these remarkable three studies reveal the promise of treating cancer using engineered bispecific antibodies.

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