Antibodies are the foundation of the adaptive immune system. Therapeutic antibodies were created to treat diseases such as autoimmune, cardiovascular and various diseases that cause infection. The two main types of antibodies are monoclonal and polyclonal. Monoclonal also known as mabs are identical antibodies as they are formed by one immune cell, which have been cloned by one parent cell. Polyclonal antibodies differ as they are formed by diverse cell lines. The aim of this essay is to give in depth detail about the production of therapeutic antibodies, their molecular milestones, the limitations of clinical humanised and chimeric murine antibodies and its future prospects. Figure 1: overview of antibody structure Molecular Milestones It is prominent that there are a number of milestones, which are an essential part of the production of antibodies in today’s world.
Each step has a specific role to play in the production of therapeutic antibodies. These milestones give an insight and understanding of how therapeutic antibodies have developed over the years and how it has the ability to treat and cure diseases. The first milestone is the description of anti- sera. The aim of the first milestone was too expose healthy people to tissue that was infected with smallpox. This was used to prevent infection. Edward Jenner made this known worldwide. His work included inoculating pus that was removed from a cow. He then infected a young child by injecting it into him.
This gave the child protection to smallpox. This fascinated Louis Pasteur who then invented a human vaccine. This vaccine was made for the treatment of rabies. This method leads to the discovery of immunity to animals. Animals that were infected with disease could be cured. Healthy animals could be treated and help prevent infection. Blood was removed from rabbits which would then be transported to mice which would lead to protection against infection.
The second milestone talks about how serum therapy was developed for treatment of diphtheria and tentams. An anti-diphtheria serum was made so that humans could be vaccinated against the disease. An experiment was carried out by Ehrlich where animals were fed low doses of toxins showed that they were protected from the same toxin when given a lethal dose of that toxin.
This became known as active and passive immunization. In the 1900s the protection of antibodies against disease was discovered. This was milestone 3. A procedure where tissue culture of spleens from rabbits were inoculated with bacteria. This procedure showed a massive development of plasma cells connect when antigen is stimulated. Plasma cells were known as antibody producers. But for what reason? When the thymus is detached from mice its effects are catastrophic.
The will reject skin grafts from strains of different mice. And antibody responses are low. Therefore, the thymus is extremely important for the development of the immune system. Milestone 4 determines the system using antibodies to quantify insulin which is present in blood plasma. This showed the competitiveness between the binding of antibodies to endogenous insulin compared to their binding of radioactive insulin. Insulin was measured by radioimmunoassay which showed how much blood was present. Milestone 5 known as Clonal selection describes how individual antibody producing cells creates antibodies of only one specific cell. These increase in reply to the discovery of antigens.
An experiment was carried where rat cell lines were stimulated with many antigens and only one antibody is detected in the medium. Milestone 6 observed that allergies could be passed on to a healthy person if that person has received a blood donation. This is known as the pk reaction. Milestone 7 talks about putting antibodies into shape. Edelman and porter had many questions around the structure of how antibodies distinguish antigens. This interested them so much that they divided immunoglobulins into tiny pieces by chemical treatment. They observed each piece.
Edelman observed two chains of 20-24 kDa and 50-60 kDa this represented that the L and H chains are exactly the same. Which formed disulphide bridges. Limitations of clinical humanized and chimeric murine antibodies There are a number of humanized monoclonal antibodies that have been discovered. The one that shines above the rest is Herceptin. Herceptin was the first antibody that was used for clinical use. Herceptin is known for its treatment of breast cancer.
The FDA approved it in 1998. Herceptin has the ability to distinguish a cell surface receptor also known as HER2. When HER2 receptor is overproduced, breast cancer builds an incredible tolerance to chemotherapy. This tolerance is due to the epidermal growth factor, which controls whether a cell proliferates or undertakes in programed suicide by signalling a selection of intracellular proteins that add to gene expression. There have been limitations to producing human myeloma cultures for the creation of monoclonal antibodies.
It has been nearly impossible to create a human myeloma line that would meet the criteria for hybridoma production. However, research claims that ouabain-resistant human myeloma cell line has distinctive genetic markers. Ouabain-resistanthuman myeloma cell line can easily be attached with ouabain-sensitiveEpstein–Barr virus-transformed cells. as wellas with fresh tonsil and blood lymphocytes, giving rise to stable hybrids thatcontinuously secrete very large quantities of human immunoglobulins.
Thederived hybrids do not lose immunoglobulin secretion over many months ofcontinuous growth. The availability of this cell line should enable the in vitro immortalization ofhuman antibody-producing B cells that are formed in vivo. The monoclonal antibodiesproduced may have advantages in immunotherapy.