Antibody drugs are an important aspect of the field of biotechnology pharmaceuticals. Antibodies have the specificity to recognize antigens, so using antibodies to diagnose and treat diseases has long been a goal pursued by pharmaceutical researchers. The binding of antibodies to target antigens has high specificity, effectiveness, and safety, and is clinically used in various major diseases such as malignant tumors and autoimmune diseases. The development of antibody drugs is not achieved overnight, and the discovery of antibodies and the clinical application of antibody drugs have gone through a long historical process.
The earliest application of antibody therapy can be traced back to the record of Chinese people getting vaccinated with "smallpox" to prevent smallpox. The internationally recognized smallpox vaccination technique originated in China in the 10th century AD, but according to some historical records in China, smallpox vaccination began in the Tang Dynasty. However, at that time, the vaccination was only secretly circulated among the people and not made public to the world. In 1661, with the reign of Kangxi who inherited the throne due to smallpox, smallpox vaccination began to enter the imperial palace from the people, and the vaccination technique began to be promoted and popularized throughout the country. Later, Jenner, a British person, was inspired by the Chinese smallpox vaccination method and vaccinated with cowpox to prevent smallpox. Today, the development of immunology has lasted for three and a half centuries.As early as the end of the 19th century, the establishment of antibody passive immunotherapy opened up new avenues for the treatment of underdeveloped diseases at that time. Ehrlich's side chain theory laid the foundation for immunology and immunotherapy. He believes that the surface of cells has specific receptor molecules (or side chains) that only bind to specific groups in toxin molecules; If cells can survive after binding to toxins, they will produce an excess of side chains, and some of the side chains will be released into the bloodstream, which is called an antitoxin, now known as an antibody. In the late 1880s, scholars discovered the pathogenicity of diphtheria exotoxin secreted by Bacillus diphtheriae while studying pathogens, and subsequently discovered the presence of "bacteriocins" in the serum of infected individuals, which were the earliest antibodies discovered. Von Behring and his colleague Kitasato officially used diphtheria antitoxin to treat diphtheria patients in 1890, and subsequently successfully administered diphtheria detoxifying exotoxin for vaccination. At that time, scientists named the substances that could stimulate the host to produce antibodies as antigens based on the characteristics of the antibody source, making antibody research an important branch of immunology and promoting the rapid development of antibody therapy.Currently, scientists have a recognized definition for antibodies. Antibodies are immunoglobulin molecules with specific amino acid sequences that are activated, proliferated, and differentiated into plasma cells by B cells recognizing antigens, and synthesized and secreted by plasma cells. They can bind specifically to the corresponding antigens. In the early stages of antibody discovery, this specific antibody substance aroused great interest among scientists. Scientists worked tirelessly to decipher the structure of antibodies, but progress was slow due to outdated experimental conditions. Until the 1950s, scientists had a very shallow understanding of the structure of antibodies and the mechanism of antigen antibody recognition. In 1937, Swedish physicist Arne Wilhelm Kaurin Tiselius demonstrated through electrophoresis that antibodies are also a type of protein and named it gamma globulin. In 1953, British biochemist Frederick Sanger successfully deciphered the chemical structure of insulin, which is also a protein, providing direction for scientists to decipher antibody structures. The analysis of antibody structure cannot be separated from American biologist Gerald Maurice Edelman. Inspired by Sanger's analysis of insulin structure, he treated immunoglobulin G with B-mercaptoethanol, breaking it down into two chains called heavy chain and light chain according to their molecular weight. Based on this, he proposed his own antibody structure: the heavy chain and light chain fold to form a unique bag like structure, thereby recognizing antigens. In 1963, Edelman and Rodney Robert Porter (Sanger's first doctoral student) combined their years of research results to propose a relatively mature antibody molecular model. They believe that antibodies are a "Y" - shaped symmetrical structure composed of two heavy chains and two light chains, with one light chain and half of one heavy chain forming a branch of the "Y" - shaped structure. The specific binding site for antibody recognition of antigens is located at the top of the two branches of the "Y" - shaped structure, with a portion of both the light and heavy chains included.In 1969, Edelman and Porter achieved a remarkable feat by successfully sequencing over 1300 amino acids of an antibody, making it the largest protein molecule for amino acid sequencing at the time. Subsequently, Edelman continued to delve into the structure of antibodies and proposed increasingly precise antibody molecular structures, including heavy chain variable regions, heavy chain constant regions, light chain variable regions, light chain constant regions, and the positions of disulfide bonds within antibodies. He also believed that differences in antibodies were determined by differences in variable regions. Through unremitting research on the structure of antibodies, the structural basis for antibody recognition of antigens has been effectively elucidated, but the fundamental issue of antibody diversity cannot be avoided. The molecular sequence of antibodies is not fixed, and the immune system can produce different antibodies that bind to different antigenic substances. According to the theory of 'one gene encodes one polypeptide chain', even the human genome cannot meet the demand for antibody diversity coding. For this issue, Edelman and another colleague Joseph Gaily proposed the initial idea of antibody diversity production in 1967. They believe that there is chromosomal rearrangement in the genes encoding antibodies, and after recognizing antigens, a limited number of antibody genes encode an infinite variety of antibody molecules through different combinations.On the basis of Edelman's theory of antibody diversity, in 1976, Japanese scientist Toshiyuki Tone and his colleagues discovered the distribution of antibody light chain genes in embryonic cells that did not produce antibodies and in myeloma cells that produced antibodies. They found that different antibody genes were farther apart in embryonic cells, while antibody genes were closer in myeloma cells. This discovery indicates that during the development of germ cells into immune cells, antibody genes undergo a redistribution phenomenon. Based on this, Tone Chuan confirmed through a series of conclusive experimental data that antibody diversity is caused by chromosomal rearrangements and mutations of antibody bases in B lymphocytes. According to estimates, antibody genes can even encode 10 billion different antibodies through recombination and mutation, which explains the reason for antibody diversity. In 1987, Ken Tone was awarded the Nobel Prize in Physiology or Medicine for his groundbreaking research on antibody diversity.The above article is excerpted from the internet
All articles reposted on this website are for the purpose of conveying more information. Media or individuals who do not wish to be reposted can contact us and we will immediately delete them. All articles only represent the author's viewpoint and do not represent our company's position.
