Immune System Series
Frontiers in Immunology: Hybridoma Technology
Through a stratagem known as hybridoma technology, scientists are
now able to obtain, in quantity, substances secreted by cells of
the immune system-both antibodies and lymphokines. The ready supply
of these materials has not only revolutionized immunology but has
also created a resounding impact throughout medicine and industry.
A
hybridoma is created by fusing two cells, a secreting cell from
the immune system and a long-lived cancerous immune cell, within
a single membrane. The resulting hybrid cell can be cloned, producing
many identical offspring. Each of these daughter clones will secrete,
over a long period of time, the immune cell product. A B-cell hybridoma
secretes a single specific antibody.
Such
monoclonal antibodies, as they are known, have opened remarkable
new approaches to preventing, diagnosing, and treating disease.
Monoclonal antibodies are used, for instance, to distinguish subsets
of B cells and T cells. This knowledge is helpful not only for basic
research but also for identifying different types of leukemias and
lymphomas and allowing physicians to tailor treatment accordingly.
Quantitating the number of B cells and helper T cells is all-important
in immune disorders such as AIDS. Monoclonal antibodies are being
used to track cancer antigens and, alone or linked to anticancer
agents, to attack cancer metastases. The monoclonal antibody known
as OKT3 is saving organ transplants threatened with rejection, and
preventing bone marrow transplants from setting off graft-versus-host
disease.
Monoclonal
antibodies are essential to the manufacture of genetically engineered
proteins (Genetic Engineering); they single out the desired protein
product so it can be separated from the jumble of molecules surrounding
it. monoclonal antibodies are also the key to developing new types
of vaccines (Vaccines Through Biotechnology).
With
growing experience, scientists have devised several sophisticated
variants on the monoclonal antibody. For instance, they have created
some monoclonal antibodies of human rather than mouse origin; human
monoclonal antibodies can be used for therapy without risking an
immune reaction to mouse proteins. They have also succeeded in "humanizing"
mouse antibodies by splicing the mouse genes for the highly specific
antigen-recognizing portion of the antibody into the human genes
that encode the rest of the antibody molecule.
Other
monoclonal antibodies have been designed to behave like enzymes;
these so-called catalytic antibodies or abzymes speed up, or catalyze,
selected chemical reactions by binding to a chemical reactant and
holding it in a highly unstable "transition state." By, in fact,
cutting the proteins to which they bind, such antibodies may be
useful for such things as dissolving blood clots or destroying tumor
cells. Yet other researchers, by fusing two hybridoma cells that
produce two different antibodies, have created hybrid hybridomas
that secrete artificial antibodies made up of two nonidentical halves.
While one arm of the bispecific antibody binds to one antigen, the
second arm binds to another. One may bind to a marker molecule,
for instance, and the second to a target cell, creating an entirely
new way to stain cells. Or, one arm of a chimeric antibody may bind
to a killer cell while the other locks to a tumor cell, creating
a lethal bridge between the two.
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