CPM Spring 2019 - 17

daup h i n c m s .o rg

Let's imagine an analogy to help form a
An important type of cell in human
framework about what they are and what blood is the lymphocyte, and one of the
they do.  If you›re a rock fan, you might main type of lymphocytes are B cells, which
remember a story about how Van Halen function in the production of antibodies.  B
had a rider in their concert contracts stip- cells encounter antigens in the blood stream,
ulating that they have bowls of M&Ms in internalizing and digesting them.  A matchtheir dressing rooms with the brown ones ing T cell attaches to the B cell, secreting
removed.  Make believe that a concert factors that allow the B cell to mature and
promoter wanted to invent a syrup that multiply into antibody-producing plasma
would melt brown M&Ms, thus saving cells.  These cells then secrete antibodies
time individually plucking them out of against further exposure to the antigen. 
the bowls.  The first batch melted all of the Each B cell can only make antibodies with
candies.  A second trial was more successful one unique specificity for an epitome recepbut melted the green and red M&Ms along tor.  Monoclonal antibodies are produced
with the brown ones.  Finally, he was able to by a single, cloned B cell through genetic
invent a syrup that only melted the brown engineering.    Pharmacology scientists have
M&Ms.  This is similar to what monoclonal been able to develop these large, complex
antibodies do in the human body, being protein molecules, made by mammalian
very specific in leading to desired drug cells under controlled conditions, which
reactions and avoiding side effects.
can bind to  target antigens with high
specificity and affinity for a wide array
The underlying mechanism of many of diseases. They work either by directly
human diseases lies in the immune system.  blocking the cell›s receptor, or by attaching
An antigen is a substance in our bodies to ligands, which are stimulatory ions or
that can be foreign (such as a bacterium molecules that attach themselves to the
or a wood splinter) or innate (such as your receptors to cause disease.   In 2016, at
thyroid gland or pancreas).  On its surface least 69 monoclonal antibodies had been
is a receptor (also called an epitope) which approved for therapeutic use by the FDA.
can be grabbed by a protein called an antibody...think of a key being put into a lock. 
Monoclonal antibody drugs differ in
When the antibody recognizes the antigen, many ways from most other drugs that
a biologic reaction occurs that is either patients and doctors  have utilized in
beneficial (you don›t develop influenza after medicine. They are much more specific in
someone sneezes in your face, because you targeting the antigen receptors that cause
previously got a flu shot) or harmful (you disease.  By not attaching to non-desired
develop a migraine headache, arthritis or receptors, they are much lower in side
cancer, or you develop wheezing and hives effects.  Unfortunately, they are relatively
after a bee sting).
highly degradable in the GI tract, and their
large molecular size makes them poorly
Antibodies are specialized proteins called permeable, so they generally have to be given
immunoglobins, or Ig's, containing a heavy by injection (intravenous, intramuscular, or
chain fragment crystallizable region (Fc) under the skin) instead of orally.  However,
that initiates host defense mechanisms, and they have longer half-lives (length of survival
two light chain fragment antibody binding in the body) than non-genetically cloned
regions (Fab).  70% of antibodies are of medications, so they are ideally suited for
the IgG type, providing immunity against preventive therapy rather than acute care
invading pathogens.  10% are called IgM, medical needs.  Hence, they are dosed days/
involved in some of the earliest activity weeks/months apart, rather than hours
against antigens; they rise in the blood apart. When the medications are derived
stream in the first days and weeks of an from mouse DNA, their chemical names
infection.  IgE is present in very small will end with the suffix  "-omab", and if
amounts, and comes into play with overt, made partly or completely from human
and often severe, allergic reactions.
genetic material, their names will end

with "-ximab", "-zumab", or "-umab".  The
degree of human-ness does not influence
the development of anti-drug antibodies.
Monoclonal antibody drugs are currently
being increasingly used in health care.  Three
drugs are currently available for migraine
headaches, greatly decreasing headache
frequency and severity with few side effects. 
Asthma treatment now includes monoclonal
antibody meds, again lowering frequency
and severity of wheezing, thus dropping
ER and hospitalization rates.  Monoclonal
antibodies are standardly used in inflammatory arthritis conditions such as rheumatoid
arthritis and lupus.  Gastroenterologists use
them to treat colitis.  As you might expect,
they are also used in cancer treatment,
delaying and preventing the development
and spread of tumors.

In the last few
years, over
300 more
monoclonal
antibody drugs
have appeared
in various stages
of development. 
Look for many
of them to
become available
and welcomed,
to improve
our health.
 

Central PA Medicine Spring 2019 17
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CPM Spring 2019

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