Science & Technology in Action

13th Edition

Monoclonal antibodies in cancer treatment

MSD

Monoclonal antibodies are artificially produced antibodies designed to target and bind to specific antigens. They are use to treat specific conditions such as: arthritis, asthma, B-cell chronic lymphocytic leukemia, breast cancer, colorectal cancer, Crohn’s disease, dermatitis, melanoma, multiple sclerosis, psoriasis and many more.
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What are antibodies and antigens

Antibodies are molecules produced by the body’s immune cells in response to the presence of an antigen. An antigen is a foreign molecule recognised by an antibody; antigens can be bacteria, virus, fungi or allergens. An antigen may be a protein expressed on a cell membrane or a toxin produced by a bacteria. An antibody recognises a specific small region of an antigen (known as an epitope). In the case of a protein antigen the region is in the range 5-12 amino acids, these amino acids may be in a continuous linear stretch in the primary sequence or the epitope may be created upon folding of the protein into its tertiary structure. When an antigen enters the body it elicits an immune response resulting in the production of antibodies by B-Cells. A typical healthy adult body has thousands of antibodies all specifically recognising different antigens and their epitopes. An antibody binds to an antigen with high affinity and this is referred to as an antibody- antigen complex (Goldberg Theory). There are several types of antibodies (IgA, IgD, IgE, IgG and IgM), each antibody specifically recognises a particular type of antigen. For example IgE antibodies are produced in response to an allergen (pollen) in the lungs and skin, IgG antibodies are produced to prevent infection and are found circulating in the blood. The role of the antibody is to bind to the antigen, inactivating it so immune system processes can take over and destroy it. Antibodies’ specificity for binding a unique epitope/antigen is a property exploited for many uses such as in the treatment of diseases and cancers, in medical diagnostics and in the scientific research in laboratories.

Monoclonal antibodies

Monoclonal antibodies (mABs) (mono from the Greek meaning one) are antibodies produced from an identical B cell which specifically only recognise a single epitope in contrast to Polyclonal antibodies which recognise multiple different epitopes. Monoclonal antibodies were first produced in laboratory environment by Kohler and Milstein in 1975. They exposed mouse immune cells to an antigen, stimulating production of specific antibodies. These immune cells were then fused with myeloma cells, forming hybridoma cells. Myeloma cells are immortal – they are cancer cells which replicate indefinitely. Small cell samples were taken from the hydridoma cell culture and their antibody production monitored. Cells showing strong stable production of the antibody were further isolated and cloned. This ability to produce antibodies in laboratory environment ledeventually to industrial-scale antibody production.

True or False?

  1. Monoclonal antibodies are only useful for cancer therapy. false
  2. Monoclonal antibodies have been used in conjunction with other therapies for cancer treatment. true
  3. A large antigen molecule can usually combine with more than one type of antibody. true
  4. Antigens and antibodies are protein molecules. true
  5. Antibodies injected into a person may themselves provoke an immune response. true
  6. Tumours often develop resistance to initially effective therapy. true
  7. Tumours that depended on one gene for their formation may lose that dependence as the cancer progresses. true
  8. To date, monoclonal antibodies have been more successful with some cancers than with others. true
  9. Proteins located inside a cancer cell are very useful targets for attack by antibodies. false
  10. All mutations in cells result in the development of cancer. false

Glossary of terms

Adjuvant
a substance that improves the effectiveness of a drug or vaccine, but has no direct effect on its own
Alemtuzumab
a drug used in the treatment of chronic lymphocytic leukemia (CLL) and T-cell lymphoma
Amino acid
the organic molecular sub-units of proteins
Antibodies
Proteins produced by lymphocytes in response to a particular antigen
Antigen
a chemical that stimulates the specific immune system to produce antibodies
B cell
a type of white blood cell (or lymphocyte) which produces antibodies as part of the adaptive immune system
biospecific monoclonal antibodies
combination of two monoclonal antibodies, each of them binds to a different compound
Cancer
a disease caused by the uncontrolled growth of tissue, leading to the production of malignant cells
Checkpoints
immune system checkpoints are
Chemotherapy
the use of toxic chemicals to destroy cancer cells
Chimeric antibodies
antibodies that contain amino acid sequences of one species in one region and sequences from a different species in another
Clone
a group of genetically identical organisms
Conjugated monoclonal antibodies
monoclonal antibodies with a therapeutic agent (radioactive or chemotherapeutic) attached
Constant or effector region
antibodies have two sections: i) the constant or effector region that binds immune cells, and ii) the variable region that binds antigens
DNA
deoxyribonucleic acid - double helix molecule that contains the hereditary information that is passed from parent to offspring; the activity of living cells is controlled by the DNA within them
Fluorescent
substances that absorb electromagnetic radiation and emit the energy at a lower frequency
Genetic engineering
artificially altering the DNA of cells
Genomics
study of the genome and the interactions of the genes it contains
Hormone
a chemical messenger within the body that is secreted by one type of cell and acts on another type of cell.
humanised monoclonal antibodies
a monoclonal antibody whose amino acid sequences outside of the antigen-bonding site have been replaced by sequences of human origin
hybridoma
a clone of hybrid cells formed by the fusion of normal lymphocytes and melanoma cells, used to produce monoclonal antibodies
immortal
cells which multiply indefinitely are said to be immortal
immune system
the body's system of defences against disease - composed of certain white blood cells and antibodies.
Leukaemia
uncontrolled production of abnormal leucocytes (white blood cells) by the bone marrow
Metastasis
migration of cells from a cancer growth to form new growths elsewhere in the body
Monoclonal antibodies
antibodies that are identical because they are produced by identical immune cells. They can be used to detect a specific antigen.
Mutate
to change the structure of a gene in a way that can be inherited
Myeloma
cancer of a type of white blood cell that normally produces antibodies
Naked monoclonal antibodies
pure monoclonal antibodies which act alone
Phage
a virus that infects bacteria
Proteomics
study of the structure, functions and interactions of proteins
Radioactive
emitting radiation that is ionising, i.e. either subatomic particles or electromagnetic waves whose energy is greater than that of visible light (UV, X-ray, gamma rays)
T cells
white blood cells that are involved in rejecting foreign tissue, regulating immunity and controlling the production of antibodies to fight infection.
Tumour
a swelling especially due to an abnormal growth of tissue
Virus
a very small disease-causing particle containing DNA which when it enters a cell typically redirects the cellular mechanism to produce more virus particles