Antibodies are proteins that are produced by our immune system to target specific foreign object that are referred to as antigens. Monoclonal antibodies (mABs) are antibodies that are produced by cloning natural antibodies derived from single B cell
These monoclonal antibodies have very high affinity for their respective epitopes (protein binding site). Currently monoclonal antibodies are being widely used for research and therapeutic purposes. The extensive use of monoclonal antibodies is owing to their monospecificity to bind with and target specific proteins or cells.
Production of monoclonal antibodies
For the production on monoclonal antibodies first the selected animal is injected with desired antibody which stimulates their immune system. B lymphocytes, which are antibody producing cells, are then harvested from the spleen. Hybrid cells or hybridomas are then created by fusing these cells with immortal myeloma cell line.
From these hybridomas those are selected that have specificity towards our desired target. The selected hybridomas are then cloned giving rise to hybridoma colony which is maintained in a culture media to get a continuous supply of monoclonal antibodies. Every single antibody produced by this hybridoma colony has capacity to bind with specific receptor found on the surface of a cell.
Types of monoclonal antibodies
There are generally four types of monoclonal antibodies:
- Murine (-omab): these antibodies are those that are entirely derived from a murine source. In most cases they lead to an allergic reaction in humans.
- Chimeric (-ximab): these are the antibodies having the variable regions from murine origins while the constant regions are from human source. These can also cause an allergic reaction in humans.
- Humanized (-zumab): these monoclonal antibodies are mostly derived from a human source except for the part of which binds to its target.
- Human (-umab): these antibodies are entirely derived from a human source.
Mechanism of therapy
Monoclonal antibodies work by identifying and recognizing specific proteins on target cells, for example they can be cancer cells. Each specific type of antibody targets a specific protein. So different types of monoclonal antibodies have to be made in order to target different types of proteins or cells. Different MABs work in different ways depending on the protein that they target.
Types of therapy
Following are some of the ways by which monoclonal antibodies carry out therapeutic activities:
Block cancer cell’s growth receptors
The uncontrolled division of cancer cells is usually because of large amount of growth factor receptors present on cell surface. They help the cell to survive and divide in an uncontrolled manner.
Some monoclonal antibodies target these growth factors and stop them to work properly by either blocking the signals or receptors. In this way cancer cells no longer receives the signals to divide and results in their death.
Targeted cancer drug delivery
Some monoclonal antibodies are used to selectively delivering radioactive substance or drugs directly to cancerous or other defected cells. These types of MABs are referred to as conjugated monoclonal antibodies.
Facilitating immune system
Some monoclonal antibody drugs are type of immunotherapy. They help to facilitate the action of immune system so that it can be in a better position to fight against the illness. Following are some of the ways by which they can perform their action:
- They might block the proteins that are hindering the action of immune system. Such type of monoclonal bodies are referred as checkpoint inhibitors.
- They can also attach to cancer cells to that it is easier for immune system to identify these cells. This process is referred to as antibody-dependent cell-mediated cytotoxicity.
Monoclonal antibody treatment can be carried out by injecting them either as subcutaneous injection or in the form of drip infusion in a vein. In some cases the first treatment is usually carried out by delivering them through vein and then further treatments are carried out by injecting them under the skin.
Applications
Monoclonal antibodies have found its application in both research and medicine:
Following are the applications of monoclonal antibodies in the field of research:
- Study of changes in molecular conformation
- Analysis of phosphorylation state
- Protein-protein interaction studies
- In structural analysis such as X-ray crystallography
- To identify single members of protein families
In field of medicine and therapy monoclonal antibodies are applicable:
- In cancer diagnosis and treatment
- For prevention of allograft rejection
- In neoplastic and hematopoietic disease therapy
- To treat myocardial infarctions
- In the reversal of drug toxicity
Merits
- Monoclonal antibodies are homogenous and consistent.
- They can be renewably generated once a suitable hybridoma is developed.
- Monoclonal antibodies are highly sensitive to small changes in both salt concentration and pH.
- They can be easily tested for cross-reactivity
- Though expensive, monoclonal antibodies are cheaper to develop than conventional drugs because they are based on tested technology.
- Side effects can be treated and reduced by using mice-human hybrid cells or by using fractions of antibodies.
- They are used in different ways.
- They bind to specific diseased or damaged cells needing treatment.
Drawbacks
Some drawbacks of monoclonal antibodies are as follows:
- The mono-specificity of MABs limits their applications
- Minor changes in antigen epitope structure affect the function of monoclonal antibodies
- Their production should be very specific to the antigen to which it needs to bind.
- They are not suitable for use in assays such as hemagglutination involving antigen cross-linking; slight modifications affect the binding site of the antibody
- Though these limitations can be overcome by pooling in multiple MAbs of required specificities, the identification of such MAbs can prove expensive, laborious, and time consuming.
- They are expensive.
- It is difficult to get the right antibodies and attach a compound to it.
Conclusion
Antibodies have been extraordinarily tools in laboratory research for many years. Monoclonal antibodies were developed about 25 years ago and have expanded the scope of antibodies to ex vivo diagnosis of a wide range of diseases. Scientists are taking more and more advantage of their high level of specificity and selective binding ability by employing them in immunotherapy.
The advent of hybridoma technology has led to the unlimited availability of MAbs. Numerous MAbs generated using this technology have aided the identification and analysis of tumour associated antigens from several different human melanomas, carcinomas, lymphomas, and leukemias. Literature available till date reports over 100 unique MAbs against human carcinomas.