Analysis on the Preparation and Development Trend of Monoclonal Antibodies

Currently, monoclonal antibody cloning drugs, protein drugs, gene and nucleic acid drugs, etc. are the focus of my country’s biopharmaceutical research and development. Among them, monoclonal antibody drugs, as a biologically targeted drug with unique advantages, have high specificity, strong targeting and the characteristic of low toxicity and side effects is remarkable in treating diseases.

Monoclonal antibodies are highly uniform antibodies that are produced by a single B cell clone and only target a specific epitope. With the continuous development of antibody technology and the continuous emergence of new antibodies, monoclonal antibody drugs have become the most developed in the pharmaceutical industry. One of the fast areas. Some studies have shown that in the field of biopharmaceutical R&D, one-quarter of the biotech drugs currently being studied are monoclonal antibody drugs. During this period, various monoclonal antibody derivatives have emerged, including antibody drug conjugates, small Molecular antibodies, bispecific antibodies, etc. Medicilon is a comprehensive biomedicine research and development service company. It has established a compound synthesis, compound activity screening, structural biology, pharmacodynamic evaluation, pharmacokinetic evaluation, toxicology evaluation, formulation research and new drugs in Shanghai. Registered as an integrated technical service platform in line with international standards.

Preparation of monoclonal antibodies

Traditional monoclonal antibodies are usually prepared by hybridoma technology. Hybridoma antibody technology is based on cell fusion technology by fusing sensitized B cells that have the ability to secrete specific antibodies and myeloma cells that have the ability to proliferate indefinitely. B cell hybridoma. A single hybridoma cell with this characteristic is used to cultivate a cell population to prepare a characteristic antibody against an epitope, that is, a monoclonal antibody.

Hybridoma technology makes murine monoclonal antibodies widely used in the diagnosis and research of human diseases, establishing the first milestone in therapeutic antibodies. With the development of biological technology and the elucidation of antibody gene structure, the use of recombinant DNA technology and antibody library technology to humanize murine monoclonal antibodies, chimeric antibodies, humanized antibodies, and fully human antibodies have appeared successively. Different angles overcome the shortcomings of murine monoclonal antibody clinical application, and make antibody preparation technology enter a new era.

Through genetic engineering, the monoclonal antibody and the antibody molecule in the human body have as similar characteristics as possible, and the antibody is humanized. From mouse to fully human, monoclonal antibodies have gradually reduced the probability of human anti-mouse immune response in patients, and the therapeutic effect and safety have gradually improved. Therefore, fully human monoclonal antibodies are the development trend of monoclonal antibodies. However, as the degree of humanization increases, the affinity of monoclonal antibody products will gradually decrease. Therefore, improving the affinity of monoclonal antibody products while ensuring the elimination of human anti-mouse reactions is a core technical barrier for the development of monoclonal antibody drugs.

The development trend of monoclonal antibodies

(1) Phage display technology has become the mainstream of human monoclonal antibody screening. With the deepening of the humanization of monoclonal antibodies, phage display technology (using PCR technology to amplify a complete set of antibody heavy chain variable region (VH) and light chain variable region (VL) genes from human immune cells, Large-scale monoclonal antibody screening platforms, which are cloned onto phage vectors and expressed in the form of fusion proteins on the surface of their shells, have received increasing attention. This technology can not only obtain fully human monoclonal antibodies, but also does not require cell fusion. The test cycle is short and the process is simple. It is a major breakthrough in human antibody preparation technology. At present, the international mainstream monoclonal antibody manufacturers use phage display technology to screen monoclonal antibodies.

(2) Expression culture technology is the key to monoclonal antibody production and quality control. Expression method, reactor scale, expression system and expression volume are important indicators for judging the level of enterprise technology.

(3) Separation and purification technology is the last key link in the production of monoclonal antibodies. Generally, ammonium sulfate precipitation, ion exchange chromatography, protein-Sepharose affinity chromatography and other methods are used to purify monoclonal antibodies in the industry. The yield will be reduced by 13%, so while ensuring the purity, increasing the yield as much as possible is also an important part of testing the production level of the enterprise.

At present, most of the research work of monoclonal antibody drugs has focused on the development of improved antibodies against known molecular targets related to asthma, leukemia, non-small cell lung cancer and multiple sclerosis. In the near future, the next generation of antibodies with improved performance (including ADC and bsAb) as Biobetter antibody therapy is expected to be welcomed.

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