Antibody engineering, as an important component of modern biotechnology, has made significant progress in the fields of life sciences, medicine, and drug development in recent years. Through recombinant DNA and protein engineering techniques, antibody engineering finely processes and recombines antibody genes to produce antibody molecules with specific properties and functions. These novel antibody molecules not only retain the specificity and primary biological activity of natural antibodies, but also enhance their potential application value by removing or replacing unrelated structures. This article will provide a detailed introduction to the technical principles, development history, technical characteristics, and application prospects of antibody engineering.

1、Principles of Antibody Engineering Technology

Antibody engineering is the process of processing, modifying, and recombining antibody genes using recombinant DNA and protein engineering techniques. Specifically, this technology modifies antibody genes through gene manipulation techniques such as point mutations, gene splicing, and gene deletions, and then introduces the modified genes into appropriate receptor cells for expression. In addition, antibody molecules can be further modified through methods such as cell fusion and chemical modification. These antibody molecules modified through antibody engineering are novel antibody molecules that are reassembled based on human design, capable of retaining or increasing the specificity and primary biological activity of natural antibodies while removing or reducing unrelated structures.

An antibody is an immunoglobulin (Ig) composed of four polypeptide chains, including two light chains (L chains) and two heavy chains (H chains). Light and heavy chains are connected by disulfide bonds to form a symmetrical structure. The amino terminus (N-terminus) of each chain undergoes significant changes in approximately 110 amino acid sequences, known as the variable region (V region), while the carboxyl terminus (C-terminus) is relatively stable, known as the constant region (C region). The high variability region (HVR or CDR) in the V region has high variability and is a key area for antibody antigen binding.

2、The Development History of Antibody Engineering

The development of antibody technology has gone through three important stages, from polyclonal antibodies to monoclonal antibodies, and then to genetically engineered antibodies.

First generation antibodies (serum polyclonal antibodies): As early as the early 20th century, the effects of serum antibodies and bacterial toxins were discovered and used to treat various diseases. Serum polyclonal antibodies have broad-spectrum properties and can recognize multiple antigenic epitopes, but their immunogenicity and heterogeneity limit their applications.

Second generation antibodies (monoclonal antibodies): In 1975, German scholar Kohler and British scholar Milstein collaborated to establish hybridoma technology, making the preparation of monoclonal antibodies possible. This technology utilizes cell fusion technology to fuse immune B cells with myeloma cells, forming hybridoma cells that can secrete specific antibodies and proliferate infinitely. Monoclonal antibodies have high specificity and uniformity, greatly promoting the development of immunology, genetics, microbiology and other fields.

Third generation antibodies (genetically engineered antibodies): In the 1980s, with the continuous development of DNA recombination technology and protein engineering technology, people began to use these technologies to modify antibody genes and produce genetically engineered antibodies. Genetic engineering antibodies retain the specificity and main biological activity of natural antibodies, while removing irrelevant structures, making the performance of antibodies more superior.

3、Technical characteristics of antibody engineering

1. Reduce immunogenicity: Through genetic engineering technology, the body's rejection of antibodies can be reduced or even eliminated. For example, through humanization technology, the variable region of mouse antibodies is combined with the constant region of human antibodies to produce human mouse chimeric antibodies, greatly reducing their immunogenicity.

2. Improve penetration: The molecular weight of genetically engineered antibodies is relatively small, which can partially reduce the mouse source of antibodies and is more conducive to penetrating the blood vessel wall and entering the lesion core. This characteristic makes genetically engineered antibodies have broad application prospects in fields such as tumor therapy.

3. Preparation of new antibodies: New antibodies with specific structures and functions can be prepared according to treatment needs. For example, through antibody conjugation technology, antibodies can bind with drugs, toxins, etc. to form antibody drug conjugates (ADCs), thereby improving the targeting and efficacy of drugs.

4. Multiple expression modes: Genetic engineering antibodies can be expressed in various ways such as prokaryotic cells, eukaryotic cells, and plants, expressing antibody molecules in large quantities and greatly reducing production costs. This enables genetically engineered antibodies to have higher economic benefits in drug development and industrial production.

4、The application prospects of antibody engineering

1. Drug development: Antibody engineering has enormous potential for application in the field of drug development. Antibody molecules modified through antibody engineering can be used to design highly efficient, low toxicity, and highly specific antibody drugs targeting specific disease targets. For example, in tumor treatment, antibody drugs can specifically recognize and kill tumor cells while reducing damage to normal cells. In addition, antibody drugs can also be used for the prevention and treatment of various diseases, such as viral infections and autoimmune diseases.

2. Tumor treatment: In the field of tumor treatment, the application of antibody engineering is particularly prominent. By modifying antibody molecules, they can have stronger targeting, higher affinity, and longer half-life, thereby improving therapeutic efficacy and reducing side effects. For example, trastuzumab (trade name Herceptin) is a humanized monoclonal antibody against HER2 positive breast cancer, which can specifically bind HER2 receptor and inhibit the growth and proliferation of tumor cells. In addition, antibody coupled drugs (ADC) such as Kadcyla (T-DM1) combine trastuzumab with cytotoxic drugs to achieve precise treatment of HER2 positive breast cancer patients.

3. Autoimmune diseases: Autoimmune diseases are diseases caused by the immune system mistakenly attacking its own tissues. Antibody engineering also plays an important role in the treatment of autoimmune diseases. For example, Infliximab is a fully humanized monoclonal antibody against TNF - α (tumor necrosis factor alpha), widely used to treat various autoimmune diseases such as rheumatoid arthritis and Crohn's disease. It can specifically bind and neutralize TNF - α, thereby reducing inflammation and tissue damage.

4. Infectious diseases: Antibody engineering also plays an important role in the prevention and control of infectious diseases. By modifying antibody molecules, antibodies with broad-spectrum neutralizing activity can be designed for the prevention and treatment of viral infections. For example, researchers are actively developing antibody therapy for viral diseases such as HIV, Ebola virus and COVID-19. These antibody therapies include monoclonal antibodies, antibody cocktail therapies, and combinations of antibodies and antiviral drugs, aimed at improving treatment efficacy and reducing the risk of viral mutations.

Antibody engineering will continue to play an important role in fields such as life sciences, medicine, and drug development. With the launch of the Beacon Optofluidic System by Redbert (Beijing) Biotechnology Co., Ltd., it can save you a lot of screening time and greatly reduce production costs. The conventional use of hybridoma or phage display technology usually takes 3-6 months, but the Beacon Optofluidic System device can obtain specific antibody sequences in just 3 days. Single plasma cells can be directly isolated and detected in a 0.5nl system, from which target cells expressing specific antibodies can be screened, and their heavy and light chain mRNAs can be obtained. These mRNAs can be directly used for sequencing and optimization after reverse transcription. In the future, antibody engineering is expected to play an important role in more fields such as precision medicine, personalized treatment, and disease prevention. By continuously optimizing and innovating antibody engineering technology, humans will be able to develop more efficient, safe, and convenient antibody drugs and treatment methods, making greater contributions to the health and well-being of all humanity.

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