Antibodies play an important role in the development of modern medicine, whether in clinical treatment of patients or in basic research by scientists. In the early stage of antibody production, it is inevitable that animals must be sacrificed in exchange for sufficient antibody, and the quality is not stable. Nowadays, due to the advancement of biotechnology, a large number of antibodies can be produced by using microorganisms or in vitro cultured cell lines, called recombinant antibodies, which not only do not require killing but also have many advantages.
Importance of Antibodies for Medical Development
Antibodies are the core components of many screening reagents and anti-cancer drugs. Without antibody screening reagents, it is like a computer with a CPU removed and only an empty shell remains, which is like scrap iron. Antibodies are also a research tool that biomedical scientists rely on in their basic research. Biologists who lack the assistance of antibodies are like explorers without a compass, and the possibility of getting lost is greatly increased. The application field of antibodies continues to expand, and the demand will continue to grow in the future. How to reduce the cost of antibody production and improve the efficiency is an urgent development direction.
How antibodies fight pathogens
Antibodies are proteins produced by the vertebrate immune system against invading harmful pathogens such as bacteria, viruses, etc. Because antibodies can specifically identify specific pathogens, they can guide immune cells to launch precise attacks without harming innocent people. In addition, when the antibody recognizes the pathogen, it will bind to it very closely and “surround” it, so the antibody itself is sufficient to neutralize the pathogen’s toxicity and prevent harm to the human body.
recombinant antibody
Antibodies, like other proteins, are first transcribed from genes into mRNAs and then translated into proteins. Today, scientists have thoroughly studied the structure and genes of antibodies, and have the ability to use microorganisms or in vitro cultured cells to express antibody genes to produce antibodies. The recombinant DNA of antibodies must be constructed in microorganisms using genetic engineering technology, so the antibodies obtained are called “recombinant antibodies”.
Antibodies are widely used
The ability of antibodies to specifically identify antigens is very valuable, so they are used in the development of drugs and reagents such as biochemical testing, disease screening, stem cell separation, and purification of specific proteins. The following describes the application of antibodies in three fields.
1. Medicines to treat diseases
Many of the drugs that have been marketed use antibodies as their active ingredients, such as “Avastin” for the treatment of colorectal cancer, breast cancer and non-small cell lung cancer, “Unnecessary” for rheumatoid arthritis and chronic lymphocytic leukemia. Cancer” (Rituximab) and cancer immunotherapy drug “Keytruda” (Keytruda). The global antibody drug market will reach US$178 billion in 2021 and is estimated to be as high as US$450 billion in 2028, which is about the total budget of the Taiwanese government in five years.
2. Disease and health check
The most important component of the recently widely used new coronary pneumonia (antigen) rapid screening reagent is the antibody that can recognize the new coronavirus protein. The key ingredient of the pregnancy test is to identify antibodies to a hormone (human chorionic gonadotropin), which increases during pregnancy and can accurately test for pregnancy. Other screening tests such as liver B, colorectal cancer, and ovarian cancer also rely on various specific antibodies.
3. Isolation of stem cells and immune cells
Regenerative medicine and cancer cell therapy use stem cells or immune cells to help patients repair tissue or destroy cancer cells. But before treatment, doctors must first isolate useful stem cells or immune cells from the complex cells of human tissue. Cell isolation often utilizes antibodies that recognize specific cell surface proteins to help remove unwanted cells or capture specific target cells.
Humane issues of producing antibodies in animals
Because only vertebrates produce antibodies in nature, early antibody production is to inoculate animals with the target antigen to stimulate the animal to produce antibodies that recognize the target antigen. Animals that often produce antibodies include rabbits and goats. In Europe alone, the annual production of antibody animals was as high as 1 million. In order to increase animal antibody production, animals usually need to be vaccinated several times. After human beings have experienced the baptism of the new crown vaccine, they should be able to understand how painful the side effects of vaccination are.
When the antibody is harvested, since the antibody is mainly present in the blood of the animal, in order to obtain the maximum amount of antibody, the animal must be “bleed” by “cardiac puncture” until the blood is drained. Although the process fully complies with animal welfare norms, and the animal must be anesthetized first, animal life is sacrificed anyway, and only the use of non-animal antibody production methods can avoid various humanitarian problems.
The quality of antibodies produced by animals is relatively unstable
Antibodies produced by early animals (rabbits, goats, etc.), due to individual differences, even if the production process is completely in accordance with the SOP, the quality of antibodies produced by different batches of different animals is still different. Some individual antibodies have excellent antigen specificity, while some animal antibodies But unusable. Unscrupulous manufacturers may label unvalidated antibodies for sale (for basic research), and for antibodies with guaranteed quality, the cost will be passed on to the consumer side. Various costs are stacked, and the price of antibody drugs for clinical treatment of cancer is often millions of yuan, which is not affordable for all patients. The unstable quality of antibodies can also lead to unreproducible experimental results. It is estimated that the waste of biomedical research related materials, time and money due to antibodies in the United States is as high as 350 million US dollars per year.
Advantages of Recombinant Antibodies
Recombinant antibodies can be produced without animals, which not only makes the production process more controllable and reliable, but also does not need to be condemned by humanitarian groups. Now that the gene sequence that expresses the antibody is well known, the optimal antibody can be continuously produced with little batch variation and high yield. When the product demand increases and needs to be expanded, it can be easily achieved by simply expanding the number of bacterial strains or cell lines. It is estimated that the production cycle of recombinant antibodies can be completed in just a few weeks. As for traditional animal production, recombinant antibodies are more advantageous when there is an urgent need because it involves inoculating antigens several times and the production cycle is several months.
Epilogue
Technological progress never stops, and so does the development of antibody technology. In addition to recombinant antibodies, some scientists are working on miniaturizing antibodies to improve the penetration of antibody drugs; some scientists are trying to combine antibody drugs with chemotherapeutic drugs to become more potent anti-cancer drugs; some scientists are even developing simultaneous identification of cancer Bispecific Antibodies for cells and immune cells improve the efficiency of the immune system to kill cancer cells. It is hoped that with the rapid development of antibody technology, pharmaceutical companies can provide antibody drugs that are not only environmentally friendly and humane, but also affordable to the people, benefiting more patients.
(Source of the first image:Image by Freepik）