The Second Generation of Antibody Therapy for Tumors—Bispecific Antibodies

Current powerful tools for cancer immunotherapy include monoclonal antibodies, tumor vaccines, immune checkpoint inhibitors, CAR-T cell immunotherapy and bispecific antibody (BsAb). Especially CAR-T and BsAb have received more and more attention as new strategies of anti-tumor immunotherapy. Although BsAb has some technical difficulties in technology and industry, it is regarded as a prospective drug for tumor and cancer treatment.

• A Brief Introduction of BsAb

Bispecific antibodies are artificially engineered antibodies that can simultaneously bind two specific epitopes or proteins of interest. They have the ability to bind two different epitopes simultaneously and can play some special biological functions. BsAb mediates the killing of tumors by immune cells. Of the two antigen-binding arms, one binds to the target antigen and the other binds to the labeled antigen on the effector cells. The latter activates effector cells and targets them to kill tumor cells.

• The Advantages of BsAb

BsAb can simultaneously bind dual targets, block dual signaling pathways, play unique or overlapping functions, and effectively prevent drug resistance. What’s more, the two antigen binding arms bind different antigens, which effectively enhances the binding specificity and targeting of the antibody to cancer cells while reducing off-target toxicity. In addition, the use of BsAb can also effectively reduce the cost of treatment. Compared with monoclonal antibodies, it has stronger tissue penetration, tumor cell killing efficiency and clinical indications, and the dosage can be reduced to a minimum of 1/2000, which significantly reduces the cost of tumor treatment.

• The Preparation of BsAb

The preparation of BsAb mainly includes chemical coupling method, double hybridoma fusion method and genetic engineering. The chemical coupling method is the earliest preparation technique. Two complete IgG or antibody fragments are coupled into a BsAb through chemical coupling reagents. This technique is fast and simple, but it is easy to destroy the antigen binding site and is uncertain about safety and carcinogenicity. The double hybridoma fusion method is to synthesize two different hybridoma cells into two-hybridoma cell lines by cell fusion, and then obtain cloned cells through conventional hybridoma screening. The BsAb produced by this technology is random and low in efficiency, but has good biological activity and stable structure. Genetic engineering for bispecific antibody uses genetic engineering technology to transform antibodies to form various forms of bispecific antibodies. This technique is currently more commonly used to prepare BsAb.

“Bispecific antibody, as the latest concept in the field of antibody drugs, is regarded as the second-generation antibody therapy for the treatment of tumors.” Said an expert at Creative Biolabs, a leading company in BsAb field, “The ability to simultaneously detect several antigens or combine antigen binding sites with assay markers makes it an important target for further research in biomedicine, pharmacology and diagnostics.”

As a forward-looking technology, it faces many challenges in industrialization, such as mismatches, purification, instability of downstream processes, instability of the two antibodies and imbalance of their expression. With the advancement of technology, it’s believed that in the future, more and better strategies can be used to optimize various BsAbs, so that they have more powerful efficacy and lower side effects, and bring hope to cancer patients.