Immunotherapy



Immunotherapy is a disease treatment based upon the concept of triggering
the body's own natural defenses to fight off the disease, usually by
stimulating the immune system either locally or systemically.

Oncology represents one of the most actively researched areas of
immunotherapy, and offers the promise of new therapies for cancer, based
upon the idea of stimulating the patient's immune system to attack the
malignant tumor cells that are responsible for the disease.

Since the immune system responds to the environmental factors it encounters
on the basis of discrimination between self and non-self, many kinds of
tumor cells that arise as a result of the onset of cancer are more or less
tolerated by the patient's own immune system since the tumor cells are
essentially the patient's own cells that are growing, dividing and spreading
without proper regulatory control.

In spite of this fact however, many kinds of tumor cells display unusual
antigens that are either innapropriate for the cell type and/or its
environment, or are only normally present during the organisms' development
(e.g. fetal antigens). Examples of such antigens include the
glycosphingolipid GD2, a disialoganglioside that is normally only expressed
at a significant level on the outer surface membranes of neuronal cells,
where its exposure to the immune system is limited by the blood-brain
barrier. GD2 is expressed on the surfaces of a wide range of tumor cells
including neuroblastoma, medulloblastomas, astrocytomas, melanomas,
small-cell lung cancer, osteosarcomas and other soft tissue sarcomas. GD2 is
thus a convenient tumor-specific target for immunotherapies.

Other kinds of tumor cells display cell surface receptors that are rare or
absent on the surfaces of healthy cells, and which are responsible for
activating cellular signalling pathways that cause the unregulated growth
and division of the tumor cell. Examples include ErbB2, a constitutively
active cell surface receptor that is produced at abnormally high levels on
the surface of breast cancer tumor cells.

Antibodies are a key component of the adaptive immune response, playing a
central role in both in the recognition of foreign antigens and the
stimulation of an immune response to them. It is not surprising therefore,
that many immunotherapeutic approaches involve the use of antibodies. The
advent of monoclonal antibody technology has made it possible to raise
antibodies against specific antigens such as the unusual antigens that are
presented on the surfaces of tumors.

Herceptin is an antibody against ErbB2 and was one of the first generation
of immunotherapeutic treatments for breast cancer. Antibodies have also been
developed for the immunotherapeutic treatment of other diseases such as
rheumatoid arthritis. Remicaide for example, is an antibody against tumor
necrosis factor, a naturally occuring protein in humans that is one of the
major causes of the inflammation-related symptoms of rheumatoid arthritis.

The development and testing of second generation immunotherapies are already
under way. While antibodies targeted to disease-causing antigens can be
effective under certain circumstances, in many cases, their efficacy may be
limited by other factors. In the case of cancer tumors for example, the
microenvironment of many tumor types is immunosuppressive, allowing even
those tumors that present unusual antigens to survive and flourish in spite
of the immune response generated by the cancer patient, against his or her
own tumor tissue. Certain members of a group of molecules known as
cytokines, such as interleukin-2 also play a key role in modulating the
immune response, and have been tried in conjunction with antibodies in order
to generate an even more devastating immune response against the tumor.
While the therapeutic administration of such cytokines may cause systemic
inflammation resulting in serious side effects and toxicity, a new
generation of chimeric molecules consisting of an immune-stimulatory
cytokine attached to an antibody that targets the cytokine's activity to a
specific environment such as a tumor, are able to generate a very effective
yet localized immune response against the tumor tissue, destroying the
cancer-causing cells without the unwanted side-effects.

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