Antibody screening is a necessary step in the development of cell therapy drugs such as monoclonal antibody drugs, bispecific antibody drugs, ADC drugs, and CAR-T. Screening out high-quality candidate antibodies can greatly increase the likelihood of successful development of these drugs. Antibody drugs are the most important biological drugs besides monoclonal antibodies and recombinant protein drugs and are also a source of new biological therapies, including bispecific antibodies, cell therapies, gene therapies, ADCs, nucleic acid drugs, etc.

At present, common antibody screening methods include hybridoma technology, phage display technology, and single B cell antibody screening technology.

This article will first provide an in-depth analysis of hybridoma technology, and other techniques will be further interpreted in subsequent articles.

In 1975, the birth of monoclonal antibody technology officially ushered in the flourishing development of antibody drugs. Compared to polyclonal antibodies, monoclonal antibodies have a high degree of antigen recognition specificity and protein production uniformity. They can specifically target and bind to various pathogenic agents for disease treatment, and have potential in the field of disease treatment. The preparation method of monoclonal antibodies not only accelerates the development process of life sciences and medicine but also becomes the core technology of the modern biopharmaceutical industry. It has been widely applied in scientific research, diagnosis, antibody drug development, and other manufacturing fields, benefiting humanity in disease treatment and scientific exploration.

So far, hybridoma technology has developed very maturely and is currently the most widely used technology for preparing antibodies. Among the approved therapeutic antibodies, most of the technical routes use mouse-based hybridoma technology.

Hybridoma technology is a pivotal technique in biotechnology and immunology for the production of monoclonal antibodies (mAbs). This process first involves injecting antigens that stimulate immune responses into mice (or other mammals). A type of white blood cell, also known as B cell, produces antibodies that bind to the injected antigen. Then, these antibody-producing B cells were collected from the mouse body, and fused with immortalized myeloma cancer cells to produce a hybrid cell line called hybridoma, which has both the antibody-producing ability of B cells and the characteristic of longevity. And the reproductive ability of bone marrow tumors.

Figure 1: A general representation of the hybridoma method used to produce monoclonal antibodies. (Figure Source: Wikipedia)

Hybridoma technology, developed by Georges Köhler and César Milstein in 1975, revolutionized the field by enabling the creation of antibodies that are uniform in structure and specificity. They shared the Nobel Prize of 1984 for Medicine and Physiology with Niels Kaj Jerne, who made other contributions to immunology. The term hybridoma was coined by Leonard Herzenberg during his sabbatical in César Milstein’s laboratory in 1976–1977.[1]

Reference

[1] Milstein, C (1999). “The hybridoma revolution: an offshoot of basic research”. BioEssays. 21 (11): 966–73.

 

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