Transcript Monoclonal Antibodies - The Grange School Blogs

Monoclonal Antibodies
BAT: Explain what monoclonal
antibodies are and discuss their
uses
• Until 1975 it was not
possible to culture
lymphocytes outside
of an organism
because it was not
possible to get them
to divide.
• So lymphocytes were
only manufactured in
the body.
Georges Kohler and Cesar Milstein
• In 1975 they devised a
new method.
• It involved fusing
mouse cells from the
spleen (an organ rich in
lymphocytes) with a
type of myeloma
(cancer cells).
• Why did they choose
cancer cells?
Hybridomas
• Some of the resulting hybrids develop into
clones called hybridomas.
• Some of these combined the antibody-producing
capacity of plasma cells with the tumour cells
ability to reproduce.
• The desired clone is then isolated and used for
the industrial production of antibodies.
Major setback
• Kohler and Milstein were awarded a Nobel prize
for their work because of its important impact on
medicine.
• Problem – it was found that the monoclonal
antibodies manufactured from mouse cells
provoked an immune response if injected into a
patient.
• How has this been overcome?
• Recent techniques use
genetic engineering to
overcome this
problems.
• Monoclonal antibodies
are ‘humanized’ by
replacing much of the
antibody that triggers
the immune response
with the corresponding
human antibody
structure.
Transgenic mice
• To eliminate the need for humanisation of
the antibody, transgenic mice can be used.
In this case, a human gene is placed in the
mice so that they produce human
antibodies rather than mouse antibodies.
This raises the whole debate surrounding
the ethics of genetic engineering.
Uses of Monoclonal Antibodies
• Pregnancy test kits
• Diagnostic tools for AIDS
• Industrial production of interferon (a
chemical used to treat cancer and hepatitis)
• ADEPT (Antibody-Directed Enzyme Pro-drug
therapy).
ADEPT (Antibody-Directed Enzyme
Pro-drug therapy) - Magic bullets
1. An enzyme is attached
to the antibody and
the enzyme-antibody
conjugate is
administered to the
patient.
2. In the body the
antibody-enzyme
complex binds to the
tumour antigens
3. A prodrug is now given
to the patient
This circulates all around
the body but is only
activated by the enzyme
attached to the
antibody-enzyme
complex at the tumour
site.
4. Once activated the
prodrug becomes
cytotoxic, destroying
the cells at the tumour
site.
ADEPT – Clinical Trial
• It is a new therapy that has to go through
double blind clinical trials – what is this?
• Side effects of ADEPT – flu-like symptoms,
nausea, allergic reaction, increased risk of
infection.
Points to ponder
• After their first manufacture, monoclonal
antibodies were quickly and widely used in
diagnostic kits such as pregnancy tests.
Suggest why their use in human therapy
has been much slower.
• Discuss how the design of a clinical trial
has to consider both ethical and scientific
factors, and how these might conflict.
Check your understanding
• Why are monoclonal antibodies sonamed?
• Why is it not possible to use lymphocytes
or plasma cells directly as commercial
producers of specific antibodies?