Monoclonal Antibodies
Monoclonal antibodies are antibodies produced by a population of immune cells that all originate from the same B lymphocyte. They have monovalent affinity, meaning that they bind to the same epitope on antigens. Polyclonal antibodies, on the other hand, are produced by a variety of different immune cells and attach to different parts of an antigen; the human body typically responds to infections with antibodies that are polyclonal. The specificity of monoclonal antibodies makes them a fantastic candidate for human therapy, as they can be used to target the proteins and molecules that are characterize a condition. Monoclonal antibodies are used in diagnostics tests and treatment of autoimmune diseases such as rheumatoid arthritis and Crohn’s disease. They also present promising possibilities for treating cancer.
Illustration of Monoclonal Antibodies. (Multimedia Citation 1)
Video describing process of producing monoclonal antibodies with hybridomas. (Multimedia Citation 2)
Production of Human Monoclonal Antibodies
Production of Monoclonal Antibodies with Hybridomas
Multiple myeloma is a cancer of antibody-secreting plasma cells. Myeloma cells proliferate uncontrollably from a single mutated immune cell, meaning that they can produce large quantities of monoclonal antibodies indefinitely. However, it is impossible to specify which antibodies the myeloma cells produce. In 1975 George Kohler and Cesar Milstein developed a revolutionary technique for making monoclonal antibodies. They used a myeloma cell line that has lost both its ability to secrete antibodies and its ability to make HGPRT, an enzyme that generates purine using hypoxanthine. The myelomas were then placed in a HAT medium and fused with spleen cells for a mouse that had been immunized to stimulate the production of the desired antibody. This process created a hybrid cell called hybridoma that contains the antibody and is able proliferate indefinitely. Hybridoma cultures can be grown in vivo (inside the mice) or in vitro (in culture vessels).
Human myeloma cells generally do not grow well in culture or form stable hybridomas. Human B-cells infected with Epson-Barr virus can be grown in culture, but it is rare for these cells to have the desired specificity in antibody production. If scientists are somehow able to select for the cells producing the desired antibody, then the cells can be grown in culture for human monoclonal antibodies. Recombinant DNA techniques can also be used to obtain human monoclonal antibodies. After immunizing the mice to produce the desired antibody, mouse DNA from the part of the antibody that binds with the antigen is identified and fused with human DNA encoding the antibody. The fused DNA is then inserted into bacteria to produce part-mouse part-human monoclonal antibodies that are less likely to trigger an immune response than the murine monoclonal antibodies.
Different Types of Monoclonal Antibodies Produced.
(Multimedia Citation 3)
Illustration of Monoclonal Antibodies Fighing Rheumatoid Arthritis. (Multimedia Citation 4)
Use in Rheumatoid Arthritis Treatment
Rheumatoid arthritis is “an autoimmune disease in which your body’s immune system – which protects your health by attacking foreign substances like bacteria and viruses – mistakenly attacks your joints” (Citation 20). It causes inflammation of the joints and can harm organs. Biologic drugs containing monoclonal antibodies can be used to treat the condition by targeting the tumor necrosis factor alpha (TNFα ), interleukin-1, or cell surface molecules on T and B cells. Drugs like Remicade (infliximab) and Humira (adalimumab) are TNF blockers as they inhibit TNFα signaling. TNFα “encodes a multifunctional proinflammatory cytokine […] that is mainly secreted by macrophages” (Citation 21). Kineret (anakinra) inhibits interleukin-1, which helps to regulate inflammatory responses.
Uses in Cancer Treatment
There are two types of monoclonal antibodies used in cancer treatment. The first is naked monoclonal antibodies, which function by themselves. They are the most common type of mAbs used in cancer treatment. The other type is conjugated monoclonal antibodies, which are also attached to particles such as toxins, chemotherapy drugs, or radioactive particles. The monoclonal antibody attaches itself to the antigen and thus delivers the other substance to the cancer cell, where it can carry out its function. This limits the amount of damage done to other cells.
"When a monoclonal antibody attaches to a cancer cell, it can:
1) Make the cancer cell more visible to the immune system. The immune system attacks foreign invaders in your body, but it doesn't always recognize cancer cells as enemies. A monoclonal antibody can be directed to attach to certain parts of a cancer cell. In this way, the antibody marks the cancer cell and makes it easier for the immune system to find.
2) Block growth signals. Chemicals called growth factors attach to receptors on the surface of normal cells and cancer cells, signaling the cells to grow. Certain cancer cells make extra copies of the growth factor receptor.Extra growth factor receptors allow cancer cells to grow faster than the normal cells. Monoclonal antibodies can block these receptors and prevent the growth signal from getting through.
3) Stop new blood vessels from forming. Cancer cells rely on blood vessels to bring them the oxygen and nutrients they need to grow. To attract blood vessels, cancer cells send out growth signals. Monoclonal antibodies that block these growth signals may help prevent a tumor from developing a blood supply so that it remains small. Or in the case of a tumor with an already-established network of blood vessels, blocking the growth signals could cause the blood vessels to die and the tumor to shrink.
4) Deliver radiation to cancer cells. By combining a radioactive particle with a monoclonal antibody, doctors can deliver radiation directly to the cancer cells. This way, most of the surrounding healthy cells aren't damaged.Radiation-linked monoclonal antibodies deliver a low level of radiation over a longer period of time, which researchers believe is as effective as the more conventional high-dose external beam radiation.
5) Deliver chemotherapy to cancer cells. By combining chemotherapy drugs with a monoclonal antibody, doctors can deliver chemotherapy directly to the cancer cells." (Citation 12)