Monoclonal Antibodies
Monoclonal antibodies are a type of medicine that has changed the way we prevent and treat
diseases ranging from cancer and immune system disorders to childhood viral infections.They
are based on natural antibodies, which are proteins produced by the body to defend itself against
disease, but they are created in a laboratory and mass-produced in factories.
More than 30 years ago, the first monoclonal antibody product was licenced. Millions of people
have benefited from more than 100 such treatments since then. In the last six years,
approximately 50 of these have been introduced to the market.
This is one of the fastest-growing areas of biomedical research and a growing segment of the
pharmaceutical market.
Monoclonal antibodies work :-
They bind to their specific target while causing no harm to anything else in their path. This target
does not always represent a 'foreign intruder,' such as a virus. Antibodies can be programmed to
attach to specific molecules in the body, for example, to suppress the immune response when it
overreacts; this phenomenon, which occurs in some Covid-19 patients, is known as a 'cytokine
storm.'Monoclonal antibodies have been used safely and effectively to treat a growing number of
diseases, some of which were previously difficult to treat, due to their numerous applications.
Production:-
Production of monoclonal antibodies is a time-consuming and costly process.
First, scientists isolate the appropriate antibodies from human blood. They then replicate and
mass produce them in large quantities.
The majority of monoclonal antibodies are produced in Chinese hamster ovary cells, which are
grown in large bioreactors for 10 to 15 days. The resulting antibodies are then purified and
packaged for easy administration. This entire process takes a long time and requires expensive
materials.
Manufacturers are investigating ways to reduce production costs, such as through novel
technologies and the use of alternatives to hamster cells (such as algae, yeast, and plants), which
would change the way these drugs are made.
Application:-
The majority of monoclonal antibodies on the market are used to treat noncommunicable
diseases such as rheumatoid arthritis and cancer.
Cancer immunotherapies have saved the lives of millions of people worldwide over the
last few decades. Monoclonal antibodies have revolutionised the treatment of a variety of
cancers, including breast cancer, for which the drug Herceptin has been a game changer.
Only seven of the more than 100 licenced monoclonal antibodies are for treating and
preventing infectious diseases, despite the fact that many more are in the works,
including candidates for SARS-CoV-2, the virus that causes Covid-19.
Monoclonal antibodies have the potential to revolutionise the way we treat and prevent
infectious diseases. There are already encouraging signs.
Two experimental Ebola antibody therapies are being used successfully as part of an
emergency access programme in the Democratic Republic of the Congo.
Several antibodies that can fight different strains of HIV are also being developed.
Polyclonal Antibodies
Polyclonal antibodies are antibodies produced by various B cell lineages in the body (whereas
monoclonal antibodies come from a single cell lineage). They are a group of immunoglobulin
molecules that react against a specific antigen, each of which recognises a different epitope.
Dean and Abelseth (1973) obtained concentrated specific antibodies from hyperimmune serum
by using inactivated rabies virus (RABV)-infected mouse brain suspensions as a source of
antigens for immunisation of animals. Larger mammals are frequently preferred because they
can collect more serum. An antigen is injected into the mammal, which causes B lymphocytes to
produce immunoglobulin G (IgG) specific for that antigen.
The primary goal of animal antibody production is to obtain high-titered, high-affinity antisera
for use in research or diagnostic tests. Chickens, goats, guinea pigs, hamsters, horses, mice, rats,
and sheep are commonly used in PAb production.
Production:-
To initiate an amplified immune response, an antigen/adjuvant conjugate is injected into a
suitable animal. The animal is expected to have developed antibodies against the conjugate after
a series of injections over a set period of time. The animal's blood is then extracted and purified
to obtain the desired antibody.
Inoculation is carried out on an appropriate mammal. Adjuvants are substances that are used to
improve or enhance an immune response to antigens. Most adjuvants include an injection site,
antigen depot, and slow release of antigen into draining lymph nodes.
Many adjuvants contain or function directly as:
surfactants that promote protein antigen molecule concentration over a large surface area,
and
immunostimulatory molecules or characteristics Adjuvants are commonly used in
conjunction with soluble protein antigens to boost antibody titers and induce a prolonged
response with memory.
Such antigens are generally ineffective immunogens. Most complex protein antigens induce
multiple B-cell clones during the immune response, resulting in a polyclonal response. Adjuvants
generally improve or worsen immune responses to non-protein antigens, and there is no system
memory.
Chickens, goats, guinea pigs, hamsters, horses, mice, rats, and sheep are commonly used for
polyclonal antibody production. For this purpose, the rabbit is the most commonly used
laboratory animal. It based on;
The amount of antibody required,
The relationship between the donor of the antigen and the recipient antibody producer
(generally, the more distant the phylogenetic relationship, the greater the potential for
high titer antibody response)
The characteristics [e.g., class, subclass (isotype), complement fixing nature] of the
antibodies to be made should all be considered when selecting animals. Immunization
and phlebotomies are stressful procedures, and specific pathogen free (SPF) animals are
preferred when using rabbits and rodents. The use of such animals has been shown to
significantly reduce morbidity and mortality caused by pathogenic organisms,
particularly Pasteurella multocida in rabbits.
The size, extent of aggregation, and nativity of protein antigens can all have a significant impact
on the quality and quantity of antibody produced. To increase immunogenicity and provide T
cell epitopes, small polypeptides (10 ku) and non-protein antigens must be conjugated or
crosslinked to larger, immunogenic carrier proteins. The larger the immunogenic protein, the
better. Larger proteins, even in small amounts, usually result in better engagement of antigen
presenting antigen processing cells, resulting in a more satisfying immune response. Injection of
soluble, non-aggregated proteins is more likely to induce tolerance than a satisfactory antibody
response.
Advantages:-
Polyclonal antibodies have advantages over monoclonal antibodies. The technical skills required
to create polyclonal antibodies are not as difficult. They are relatively inexpensive to produce
and can be completed in a matter of months. Because PAbs are heterogeneous, they can bind to a
wide variety of antigen epitopes. PAbs are more likely to bind to a specific antigen because they
are made up of a large number of B cell clones. PAbs remain stable in a variety of environments,
such as changes in pH or salt concentration, making them more useful in certain procedures.
Furthermore, depending on the quantity required, PAbs can be manufactured in large quantities
in relation to the size of the animal used.
Pharmaceutical uses:-
Digoxin Immune Fab is an antigen-binding fragment of polyclonal antibodies raised to a
Digitalis derivative as a hapten bound to a protein that is used to reverse life-threatening
digoxin or digitoxin toxicity.
Rho(D) immune globulin is created by pooling human plasma from Rh-negative donors
who have antibodies to the D antigen. It is used to provide passive immune binding of
antigen, preventing a maternal active immune response that could result in newborn
hemolytic disease.
Rozrolimupab is an anti-RhD recombinant human polyclonal antibody composed of 25
distinct IgG1 antibodies that is used to treat immune thrombocytopenia purpura and to
prevent isoimmunization in Rh-negative pregnant women.
REGN-COV2 (Regeneron Pharmaceuticals) - a potential treatment for COVID-19 as well
as a means of preventing SARS-CoV-2 coronavirus infection.
