The Promise for Immunotherapy: a valuable and viable
cancer therapeutic
ABSTRACT
While cancer remains a significant issue, years of research have led to promising
discoveries in therapies that have the potential to put a stop to cancer. Currently, cancer is
most commonly treated with radiation therapy, chemotherapy, invasive surgery, or
different combinations of the three, but there is an upcoming therapeutic method that .
Immunotherapy is one of the newer methods, and using the body’s own immune system to
fight the spread of cancer, it has promise to revolutionize treatment. There is a need for
increased focus on immunotherapy for its ability to use the body of a patient to his/her
advantage without drastic external factors being applied.
INTRODUCTION
Immunotherapy, sometimes referred to as biotherapy, is a therapy that uses certain
agents of the body’s immune system to target and fight off cancer. The three types of
immunotherapy currently include non-specific immunotherapy, monoclonal antibodies,
and vaccines/cell-based therapies. Immunotherapy can be used on its own to treat cancer,
but is often used in conjunction with other methods (Gravitz 2013). While it may not be the
most effective method currently, there is much promise for this treatment to advance and
be a key player in different regimens for eliminating and treating cancer, ultimately
requiring increased focus on immunotherapy.
Brief History of Immunotherapy
The start of immunotherapy was in the late 1800s when an orthopedic surgeon and
cancer researcher, Dr. William Coley MD, noticed that some cancer patients fared better
after surgery if an infection occurred, indicating that an immune response helped the
patient. After his realization, he began treating patients by infecting them with bacteria
with only some luck. However, his work was soon overshadowed by radiation therapy,
which is currently the most common treatment for cancer (McCarthy 2006). It was not
until just over a century later in 1997 that the first FDA approved antibody treatment,
Rituximab, went into circulation. Since then, 11 more antibody therapies have been
approved along with the first cell-based vaccine, Sipuleucel-T, in 2010.
MODERN METHODS
As previously stated, immunotherapy can be split into three different forms: nonspecific immunotherapy, monoclonal antibodies, and vaccines. The first involves cytokines
and other chemicals that ignite a more general immune response. This immune response
increases the number of T cells in the body, allowing for increased immune awareness of
foreign cells. Monoclonal antibodies are proteins that bind to specific antigens. These
proteins can directly affect the cancer cell in some cases by being bound to a drug or
blocking a cell-signaling pathway that would allow growth. The antibodies can also tag the
cancer cell for destruction by the immune system. The third method of vaccines involves
using parts of cells, cancer cells, or antigens associated with the cancer cells to direct the
immune system toward attacking the tumor (Gravitz 2013).
Non-specific Immunotherapy
Non-specific immunotherapy is less developed than the other immunotherapies but
plays a crucial role regardless. It makes use of cytokines, a group of small proteins involved
cell signaling pathways. These cytokines are key when targeting cancer tumors because,
often, the environment is immunosuppressive, which allows for tumor growth even though
there are many foreign antigens on the tumor that would normally trigger an immune
response. Researchers are trying to direct cytokines to stimulate the immune system and
cause a response detrimental to tumors. There have been issues involving an overly strong
immune response causing systemic inflammation, which can be toxic, but new molecules
are being developed that combine cytokines with antibodies to make the increased
response directed specifically at tumors, eliminating the negative effects (Couzin-Frankel
2013). The success or failure of a cancer therapy can be defined by the features that allow
it to distinguish between cancer cells and normal tissue.
Monoclonal Antibodies
Monoclonal antibodies are the most popular form of immunotherapy currently,
likely because it has greatest number of treatments available. The 12 available treatments
cover multiple types of cancer including Hodgkin lymphoma, non-Hodgkin lymphoma,
renal cell carcinoma, colorectal cancer, several forms of leukemia and lymphoma, and
breast cancer. This wide range of targeted cancers gives hope to the scientific community
for furthering the spectrum of treatable cancers.
One of the most recently developed treatments, ipilimumab, targets the protein
CTLA-4, which is a protein receptor on T cells that prevents them from starting a largescale immune attack. After being discovered at the end of the 1980s, much research was
done to see if blocking this receptor would allow the immune system to fully attack a tumor
(Couzin-Frankel 2013). It was not until 2010 that Bristol-Myers Squibb reported that
several patients on the treatment that had metastatic melanoma lived an average of 4
months longer (10 months vs. 6 months) than those that did not have the antibodies. Some
of the patients even lived 2 years, which was especially groundbreaking considering that
this was the first time a treatment had extended the lives of melanoma patients in a
randomized trial (Fellner 2012).
Vaccines
Vaccines for cancer treatment are in the pipeline for immunotherapeutic cancer
treatment with the first approved treatment, sipuleucel-T for prostate cancer, being
released in 2010. There are several different methods that are used in different cancer
vaccines. One of these methods uses a mechanism that involves extracting a patient’s
dendritic cells and re-infusing them with an antigen that is specific to the patient’s cancer,
then using that as a vaccination. The dendritic cells infused with the cancer-specific antigen
present the antigen to other cells involved in the immune system, such as immature T cells,
which will then be primed to recognize the cancer cells. These cells that recognize the
cancer cell will mature and proliferate, causing a significant immune response targeted at
the cancer cells. Another method involves using oncolytic viruses, where a virus is
engineered to proliferate only in tumor tissue and causes the cells to lyse and die. This
method is being pursued diligently by many companies for the promising results it has
shown in the trials of some drugs that are in development. One interesting technique that is
being studied intensely is chimeric antigen receptor (CAR) therapy. This treatment
revolves around genetically modifying the T cells of a patient to make them target tumor
cells. Research has shown promising results with dramatic decrease in tumor size in
several different trials (June 2007).
As seen above, there is great potential for progress in the different facets of
immunotherapy, so researchers must not shy away from it or rule it out as a competitive
cancer treatment.
A COMPARISON
Modern immunotherapy is relatively young when looking at how long and the depth
at which other cancer therapies have been researched. For this reason, long-term effects of
current immunotherapeutic methods cannot be compared to those of other more
established techniques. Cancer patients take short-term side effects into strong
consideration because, for the time being, cancer remains relatively fatal, so the conditions
that will have a more immediate effect on the quality of life are factors that could influence
their selection of a therapeutic method.
One of the most common and most discussed methods, chemotherapy is the method
most known for its negative and intense side effects. Chemotherapy, literally meaning
“drug treatment”, uses cytotoxic drugs to attack cancer cells, killing or shrinking them, or
inhibiting growth. Though the reduction and attack of cancer cells is the goal, the majority
of these drugs are not specific enough to not affect the rest of the body. The most serious
and noticeable effects are on blood, hair, and digestive tract cells. When blood cells are
killed and their concentration in the bloodstream is lowered, patients are more susceptible
to infection, bleeding and bruising, and fatigue. The effects on cells in hair cause hair loss,
and these cells are similar to those found in nail beds, leading to the loss of nails. Damage to
the cells in the digestive tract can lead to oral sores, nausea and vomiting, diarrhea, and
loss of appetite, which can worsen a patient’s condition because of physical weakness
(NIH). All of these side effects can provoke uneasiness in a cancer patient seeking out
treatment. The physical burden of cancer is already enough for some, so adding side effects
from the treatment is unsettling. Though it needs further and more in-depth research,
happiness has been shown to have an effect on longevity and survival of cancer patients, so
not being intimidated by the treatment that is supposed to be helping them can help even
more (Verkooijen 2012).
The other popular non-invasive method, radiation therapy, has fewer side effects
than the aforementioned chemotherapy, but can still be daunting to patients, even in the
phrasing itself. The term radiation can have a negative connotation, paralleling it with
atomic warfare and causing cancer rather than curing it. Radiation is used to treat mostly
localized cancers, but can also be used as a treatment for skin cancer or places that at
which surgery can leave scarring. The side effects of radiation therapy are similar to severe
sunburn, being red, dry, itchy, and tender. These side effects are less serious, but if they can
be avoided, that might seem appealing to patients (NIH).
Surgery is the other most popular method, but the invasiveness of operation and
anesthesia can be off-putting. There will be scarring resulting from any incisions made, and
sometimes not all of the cancer is removed. Some patients cannot even undergo surgery
because their weakened physical state would put them in danger when under anesthesia.
For some people, this may be the most realistic and fast-acting option, but is not practical
for those in weakened physical states (NIH).
Immunotherapeutic treatments are relatively patient friendly because of their more
minimal side effects. The most common side effects that do occur, though, include
headache, muscle ache, fever, and weakness. These effects are quite tame in comparison to
the significant tolls some of the other therapies can take on the body. The delivery of
immunotherapies is also easy and does not involve any sort of intimidating heavy
machinery. Some are given intravenously or in a pill form, allowing the patient to be in the
hospital for a briefer amount of time, or even receive treatment at home (NIH). For other
treatments, the patients must remain in the hospital for the entire amount or majority of
time they are being treated, which can take be taxing not only physically, but fiscally and
mentally.
Beyond the side effects, there have been cases in which immunotherapy has proven
to be more effective than other treatments. An example of one such case is the study done
by Dudley et al. from the National Institute of Health in which patients, with advanced
melanoma that had not been responding to any other treatment, showed a significant
reduction of their cancers after receiving a new immunotherapy in combination with
chemotherapy (NIH). These results and their implications are promising for oncologists
and their hopes to expand cancer treatment and improve its efficacy.
Aside from its increasing physical success, immunotherapy should have an
increased focus because of how banal the immune system is and the decreased risk of
serious side effects. Many people are familiar with the immune system in a general manner,
especially those who spend large amounts of time on their health, like cancer patients.
Knowing that the treatment they are receiving is using their body to help eradicate or at
least hold off the cancer can be very reassuring in comparison to chemotherapy, radiation
therapy, or surgery. There is a large stigma surrounding these methods due to how they
affect the body. The potential side effects of approved immunotherapeutic treatments are
also significantly less intimidating than those of other treatments. Hair loss, brittle nails,
nausea and vomiting, sunburn like symptoms, and severe fatigue are just a few of the side
effects other treatments cause that likely plague the thoughts of cancer patients seeking
treatment (ACS). Being comfortable with a treatment is extremely important, especially in a
fragile state of health, so immunotherapy can make the emotional difficulties of cancer
somewhat easier (NIH). It is for these reasons and the examples provided above that
immunotherapy should be treated as a more valuable resource in cancer therapy and
receive more focus in research.
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