Monoclonal Antibody Isn’t Enough? Get to Know Antibody-Drug Conjugate and Bispecific Antibody

Since the first antibody drug OKT-3 was launched in 1986, more and more therapeutic monoclonal antibodies (mAbs) have undergone clinical research and been approved for marketing. The use of therapeutic mAbs for targeted therapy has become effective means in treatment of cancer, viral infection, and immune diseases.

However, in the treatment of tumors and autoimmune diseases, it is still necessary to block multiple signal pathways to avoid compensatory effects. At the same time, due to the high mutation rate of the virus, it is also necessary to combine multiple antigenic sites to prevent the virus from escaping. Combining a single target with a single biological activity is far from satisfying the application requirements. Thus with the advancement of antibody engineering technology, a large number of rising stars will appear in the field of bispecific antibodies (bsAbs) and antibody-drug conjugates (ADCs) in the future.

• ADC: combine targeting capability of antibody with cell-killing ability of drug

Antibody-Drug Conjugate (ADC) is a combination of highly targeted antibody drugs and powerful chemotherapeutics to accurately deliver drugs into tumor cells while avoiding the killing of normal cells, thereby reducing adverse reactions in the treatment process. The first ADC drug, Mylotarg, was approved for marketing in 2000. There are currently 9 listed drugs, and 5 ADC drugs have been approved since 2019. According to EvaluatePharma and Boston Consulting Group (BCG), the global ADC drug R&D market is expected to reach US$12.9 billion in 2024.

ADC drugs are currently mainly used in the field of tumor treatment. Because there are only a limited number of antigens on the surface of tumor cells, the amount of drugs delivered by ADC to tumor cells is also very limited, so the choice of ideal antigen targets is crucial. The target is required to be specifically expressed on the surface of tumor cells with low or no expression in normal tissues, or only in specific tissue types. At the same time, it should have a certain endocytosis rate and a suitable endocytic transport route.

In addition, the pharmacodynamic effects of ADC drugs mainly rely on toxin molecules, and the main role of the target is to bind the antibody, which brings the toxin molecule into the cell through endocytosis. It is not very important whether the target has a biological effect, so compared with mAbs, ADC drugs have more target options.

• BsAb: 1+1>2

Bispecific antibodies (BsAbs) are antibodies that can simultaneously bind to two different epitopes or antigens to block or activate dual target signaling pathways, and mediate immune cells to better kill tumor cells. In addition to the treatment of tumors, bsAbs are also used in the treatment of osteoporosis, hemophilia, autoimmune diseases and other fields.

Researchers are paying more and more attention to bsAbs. So far, there are 2 bsAbs available in the market and more than 200 in the clinical trials. The future for the research and development of bsAbs remains highly progressive and profitable option driven by the fact that increasing number of big and small pharmaceutical companies are allocating their resources and are collaborating with other stake holders of the industry.

• Creative Biolabs: An Expert in BsAb development

Creative Biolabs, established in 2004, is dedicated to providing high-quality antibody service to customers all over the world. Creative Biolabs is experienced in producing 5 major groups of bispecific molecules: bispecific IgGs, appended IgGs, BsAb fragments, bispecific fusion proteins and BsAb conjugates. In addition, the well-established platforms make it the best choice for production of innovative customized bsAb designs.

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