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Antibodies are the foundation of the adaptive
immune system. Therapeutic antibodies were created to treat diseases such as
autoimmune, cardiovascular and various diseases that cause infection. The two
main types of antibodies are monoclonal and polyclonal. Monoclonal also known as mabs are identical antibodies as they are formed by one
immune cell, which have been cloned by one parent cell. Polyclonal antibodies differ as they
are formed by diverse cell lines. The aim of this essay
is to give in depth detail about the production of therapeutic antibodies,
their molecular milestones, the limitations of clinical humanised and chimeric
murine antibodies and its future prospects. 

Figure 1: overview of antibody structure
 
 
Molecular Milestones
It is prominent that there are a number of milestones, which
are an essential part of the production of antibodies in today’s world. Each
step has a specific role to play in the production of therapeutic antibodies.
These milestones give an insight and understanding of how therapeutic
antibodies have developed over the years and how it has the ability to treat
and cure diseases. The first milestone is the description of anti- sera. The
aim of the first milestone was too expose healthy people to tissue that was
infected with smallpox. This was used to prevent infection. Edward Jenner made
this known worldwide. His work included inoculating pus that was removed from
a cow. He then infected a young child by injecting it into him. This gave the
child protection to smallpox. This fascinated Louis Pasteur who then invented
a human vaccine. This vaccine was made for the treatment of rabies. This
method leads to the discovery of immunity to animals. Animals that were infected
with disease could be cured. Healthy animals could be treated and help prevent
infection.  Blood was removed from
rabbits which would then be transported to mice which would lead to protection
against infection.
The second milestone talks about how serum therapy was
developed for treatment of diphtheria and tentams. An anti-diphtheria serum
was made so that humans could be vaccinated against the disease. An experiment
was carried out by Ehrlich where animals were fed low doses of toxins showed
that they were protected from the same toxin when given a lethal dose of that
toxin. This became known as active and passive immunization.
In the 1900s the protection of antibodies against disease
was discovered. This was milestone 3. A procedure where tissue culture of
spleens from rabbits were inoculated with bacteria. This procedure showed a
massive development of plasma cells connect when antigen is stimulated. Plasma
cells were known as antibody producers. But for what reason? When the thymus
is detached from mice its effects are catastrophic. The will reject skin
grafts from strains of different mice. And antibody responses are low.
Therefore, the thymus is extremely important for the development of the immune
system.
Milestone 4 determines the system using antibodies to
quantify insulin which is present in blood plasma. This showed the
competitiveness between the binding of antibodies to endogenous insulin
compared to their binding of radioactive insulin. Insulin was measured by
radioimmunoassay which showed how much blood was present.
 Milestone 5 known as
Clonal selection describes how individual antibody producing cells creates
antibodies of only one specific cell. These increase in reply to the discovery
of antigens. An experiment was carried where rat cell lines were stimulated
with many antigens and only one antibody is detected in the medium.
Milestone 6 observed that allergies could be passed on to a
healthy person if that person has received a blood donation. This is known as
the pk reaction.
Milestone 7 talks about putting antibodies into shape. Edelman and
porter had many questions around the structure of how antibodies distinguish
antigens.  This interested them so much
that they divided immunoglobulins into tiny pieces by chemical treatment. They
observed each piece. Edelman observed two chains of 20-24 kDa and 50-60 kDa
this represented that the L and H chains are exactly the same. Which formed
disulphide bridges.
 
 
 
Limitations of clinical humanized and
chimeric murine antibodies
There are a number of humanized monoclonal antibodies that
have been discovered. The one that shines above the rest is Herceptin.
Herceptin was the first antibody that was used for clinical use. Herceptin is
known for its treatment of breast cancer. The FDA approved it in 1998.
Herceptin has the ability to distinguish a cell surface receptor also known as
HER2. When HER2 receptor is overproduced, breast cancer builds an incredible
tolerance to chemotherapy. This tolerance is due to the epidermal growth factor,
which controls whether a cell proliferates or undertakes in programed suicide
by signalling a selection of intracellular proteins that add to gene
expression.
There have been limitations to producing human myeloma
cultures for the creation of monoclonal antibodies. It has been nearly
impossible to create a human myeloma line that would meet the criteria for
hybridoma production. However, research claims that ouabain-resistant human myeloma cell line
has distinctive genetic markers.

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Ouabain-resistant
human myeloma cell line can easily be attached with ouabain-sensitive
Epstein–Barr virus-transformed cells.

as well
as with fresh tonsil and blood lymphocytes, giving rise to stable hybrids that
continuously secrete very large quantities of human immunoglobulins. The
derived hybrids do not lose immunoglobulin secretion over many months of
continuous growth. The availability of this cell line should enable the in vitro immortalization of
human antibody-producing B cells that are formed in vivo. The monoclonal antibodies
produced may have advantages in immunotherapy.

 

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