Engineered Y-Shaped Antibody
Inhibitory systemic antibodies are the simplest among the others that will bend to substances reducing them to become ineffective or inactivate them. In crude form these types of antibodies consist of hyperimmune serums which are used to alleviate the symptoms of bites of a number of poisonous animals. An example of this type antibody is an antivenum produced in horses for the treatment of snake bite. Hyperimmune serum derived from patients with the disease can also be used prophylactically after exposure to different types of pathogenic viruses and therefore to treat different pathogenic viral condition like hepatitis B, AIDS, hyperimmune serum is used.
Monoclonal Therapeutic Antibodies
The second class of therapeutic antibodies is those, which capable of binding bioactive molecules and thereby reducing their effect in vivo. They are monoclonal antibodies with a number of targets. One of the major targets for this approach is systemic cytokines which are responsible for the propagation of disease like arthritis. Monoclonal antibodies when linked with the surface markers can also be used to reduce the number of specific cell types in vivo. These surface markers bound monoclonal antibodies attack the immune system causing the cell to be cleared from the circulation. Chimeric (which is derived from two sources mouse and human) mouse/human monoclonal antibody consists of two parts. First is mouse variable region and the second is a human constant region. This human constant region is specific to the beta cell marker CD20 and therefore this type of antibody is used for the treatment of systemic lupus erythematous, which is characterized by the formation of aberrant beta cells. These aberrant beta cells secret auto antibodies, which cause a number of immune problems.
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Engineering of Antibodies
This diagram shows how antibodies are engineered to be used as therapeutic antibodies
Agonistic Monoclonal Antibodies
Agonistic monoclonal antibodies are next types if therapeutic antibodies which possess the ability to influence living cells in vivo. They show their effects by upregulating cellular system by binding to surface receptor molecules of the cell. Agonistic monoclonal antibodies are structurally similar to the ligand. When they bind to the receptor molecule they mimic the ligand binding and also these antibodies have the capacity to remain in bound state with the receptor for a longer time than the natural molecule (ligand). This is only because cells find difficult to remove these agonistic monoclonal antibodies than that of natural ligands. These types of monoclonal antibodies are restricted to induce apoptosis in cancerous cells because they are powerful to initiate internal system cascades potentially catastrophic for both the cells and the organisms.
Therapeutic Application of Monoclonal Antibodies
Engineered Therapeutic Antibodies
There are lots of therapeutic inhibitory antibodies available and all are involved in downregulation of the cellular system by occupying the antigen binding sites of the receptor thus preventing the ligand binding. They may block the binding of different signals like hormones, cytokines and other cellular messenger. Because of these properties agonistic monoclonal antibodies are used for the management of some hormone dependent tumors such as breast cancer and also in the suppression of the immune system to prevent rejection after transplantation.
Therapeutic antibodies need to be carefully engineered and designed to make them effective in treatments. They should not appear as foreign to immune system otherwise they will be destroyed and cleared by the body’s immune system. Murine antibody derived from mouse can be engineered with human antibody so as to retain murine binding site and the constant region replaced by the counterpart of human antibody. So that they will not be recognized as foreign particles by human immune system and still they will have an effective binding capacity. Normal antibodies may remain up to 6 weeks in the circulation while engineered may survive much shorter time. This is because engineered antibodies still have a degree of antibody which is exposed to the human immune system. Therefore each engineered therapeutic antibody has a specific but different half life in vivo, which is of great importance in establishing baseline doses. Most of the engineered therapeutic antibodies have a certain degree of side effects and therefore they will be used only where the benefits outweigh the problem expected to be encountered.