Term Paper on History of Immunotherapy
(First
3 Pages)
History of Immunotherapy
Dated 1600 B.C. were the earliest record of treating a patient with cancer and
it comes from the Edwin Smith Papyrus. Literally, taking a knife and cutting it
out was the Papyrus documents surgical excision of a tumor. Surgical excision
was established as the primary method of treating solid tumors thirty-four
hundred years later in 1809, and remains so today.
Just one year after Roentgen first reported the use of x-rays for diagnostic
purposes in medicine, radiation therapy came into practice around 1896.
Particularly as an adjuvant therapy of solid tumors, radiation therapy continues
to have a major role in the treatment of certain tumors.
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Chemotherapy is an invention of the 20th century. Prompting further exploration,
Pancytopenia developed in soldiers exposed to nitrogen mustard gases during
World War I. Clinical trials in patients with hematologic malignancies
established the efficacy of chemotherapy, by the early days of World War II. Its
value for adjuvant treatment of solid tumors is also well documented.
William B. Coley is often credited with first recognizing the potential role of
the immune system in cancer treatment. Coley, observed that some of his patients
with sarcoma would undergo spontaneous regression of their tumor. He was an
early 20th century New York City surgeon. Coley was the first physician to
attempt to harness the power of the immune system to fight cancer. He associated
this tumor regression with antecedent bacterial infection. Actually devised a
vaccine consisting of killed bacteria to prompt tumor killing and he
deliberately infected cancer patients with bacteria. Complete tumor regression
was achieved in some patients.
However, it was possible not until 1976, to more fully understand how tumor
recognition and rejection was mediated at the cellular and molecular level.
Known today as interleukin, in 1976, T cell growth factor was identified and
cloned. It was then possible to study T cells in an ex vivo laboratory
situation. Cytokines such as interleukin are now established agents for the
treatment of tumors. We have explored their potential role in cancer therapy, as
we have discovered more of the cells and molecules of the immune system. (T Aso,
WE Lane, JW Conaway, RC Conaway, 269: 1439-1443)
Introduction
Cancer represents a major challenge to medical research and continues to be the
second commonest cause of death in the industrialized world. In modern cancer
therapy, cancer immunotherapy is among the most promising new approaches.
Designed to prevent or delay the formation of metastases, Igeneon is developing
immunotherapeutics with broad applicability.
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Cancer - The Disease
Cancer is the second commonest cause of death in the industrialized world, with
25% of all fatalities. Close to 44% for men and 38% for women is the lifetime
probability of being diagnosed with cancer. There are 8.1 million initial
diagnoses of cancer every year. Having made progress in the last decade,
surgical intervention and radiotherapy are the standard therapies chemotherapy
and have resulted in a significant improvement in survival rates with some forms
of cancer, but for the last 25 years the average five-year survival rate hovers
round the 60% mark (M. Bernues, C. Casadevall, R. Miro, M.R. Caballin, H.
Villavicencio, J. Salvador, A. Zamarron, and J. Egozcue, 1995).
The Immunotherapy Approach
The human immune system in general develops lifelong resistance to them, but it
fails to combat cancer successfully and it also swiftly fights off infectious
diseases. The Director of the Center for Cancer Drug Discovery & Development at
the well renowned Cleveland Clinic in Ohio, Professor Ernest C. Borden, USA sums
up as follows: "The problem is that the immune systems of cancer patients react
too weakly to tumors. Tumor cells resemble the body's own cells too closely."
“Traditional cancer therapies are primarily focused on reductions in solid tumor
mass. Cancer immunotherapy - the basic science underlying all igeneon products -
adopts a new and different approach. By the time cancer is diagnosed and
traditional therapies are applied, individual tumor cells have often already
spread to other organs (disseminated tumor cells) and result in the formation
and spread of metastases, often only after an interval of many years. Metastases
are the main cause of mortality in cancer. The main target of immunotherapy is
therefore a disseminated cancer cell, with the aim of preventing or delaying the
formation of metastases”. (P. Bernades, G. Molas, P. Beaugrand, M. Camey, M.
Denis, and R. Dupuy, et al., 2813-2818)
Active Immunization
The aim of active immunization is to elicit an immune response from the
patient's own immune system and to stimulate the production of antibodies and
the consequent destruction of tumor cells. Antibodies are proteins that use a
lock and key mechanism to dock to specific antigen substances. igeneon's
vaccines consist of exogenous antigens (protein compounds), which are exactly
similar to parts of the tumor cell membrane. One of the immune system’s
responses to the vaccines is to produce antibodies to destroy these cells. This
can help to prevent the formation of metastases and if metastases are already
present can retard the advance of the disease. The aim is to extend life
expectancy without further detracting from quality of life. (P. Anglard, E.
Trahan, S. Liu, F. Latif, M.J. Merino, M. Lerman, B. Zbar and M. Linehan,
348-356)
Passive immunization
In many situations, there is no time to wait for the immune system to produce
antibodies as a response to immunization. igeneon has therefore developed
additional specific antibodies, which correspond to human antibodies and can be
introduced in therapeutic quantities intravenously as a replacement for the
missing immune response.
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