Theresa Miorin

Professor Campbell
URWT 1103
April 11, 2016
Is Your Immune System Ready to Square Up Against Cancer?
Maybe have this bolded and underlined for more distinction as the title
Is there ever going to be a cure for cancer? Maybe, maybe not. Researchers have spent
years investigating cancers various parts, ranging from looking at it from environmental stresses
and more recently, looking at it genetically. Whenever there seems to be a new breakthrough in
finding a possible cure, one thing leads to another and there is a mishap. One step forward, two
steps back. It seems that as we become more educated in cancer, the more we realize how little
we actually know about the disease. So if there seems to be little hope, what is the point of
continuously spending thousands, if not millions, of dollars on cancer research? The answer lies
in every person who has been affected by this killer. And if Im not mistaken, I wouldnt be
surprised if every person was somehow affected by the disease, either directly or indirectly.
That is exactly why researchers and scientists are still looking for new therapies and possible
ways for a cure. Because even though one treatment might be a total flop, it can still produce
information or lead to a new discovery that could be the next big thing in cancer research. And
right now, one of those new treatments is immunotherapy, or harnessing ones own immune
system to fight back. We were all given an immune system to naturally fight disease, so why not
use it wisely? New research has been conducted looking at immunotherapy, specifically at T

cells, which are essential for human immunity. So what are these and how can they help us fight
back?
The human body has been shown to be capable of outstanding processes that function to
keep us healthy and ensure the body is working at its best. One such system is the immune
system. The National Institute of Allergy and Infectious diseases regards it as a network of
cells, tissues, and organs whose sole purpose is to protect the body from infectious diseases.
There are two different ways of fighting back in the immune system. The first is through innate
immunity where the cells will use genetically encoded receptors that will recognize any patterns
that could be dangerous to the body. These cells can recognize bacteria, viruses, fungi, as well as
others. In general, these cells primarily function to recognize anything out of the ordinary in the
body and to respond quickly when something arises, typically with inflammation. The second
form of immunity is adaptive immunity, where B and T cells arise. This is a more specialized
from because the cells bear unique receptors that will recognize specific signals. The receptor
will recognize an antigen, then activate the B or T cell, which will then divide and disperse to
address the problem. A B cells main function is to make antibodies, which will neutralize the
pathogens making them harmless. T cells are more specialized because they kill infected cells,
as well as activate and recruit other immune cells. Once these immune cells are used and the
problem is solved, the cells will be retained in the body as memory cells, so if the problem arises
another time, the memory cell can quickly activate and be used to fight against the pathogen
(Immune System).
When beginning the process of immunity, T cells are seen as highly important. These
cells circulate throughout our bodies to search for any abnormalities and infections that can cause

disease. According to the Beginners Guide to T Cells, they can be divided into two groups: killer
T cells and helper T cells. Killer T cells are described as having X-ray vision due to their
capability of seeing inside the cells by scanning their surface. This allows the killer T cells to
destroy any cells that are infected or have become cancerous. Helper T cells orchestrate the
immune response by helping B cells secrete the antibodies and microphages, as well as activate
cytotoxic T cells to kill the infected target cells (Beginners Guide to T Cells). Because T cells
can be described as our own little defense mechanism against any bacteria or viruses that enter
our body, many scientists and researchers have begun the process of immunology, or the process
of using the immune system to fight back diseases. The T cells already protect us from disease,
so why not utilize them for our benefit? Through various studies and trials, the process of
immunology and T cell use has been thoroughly looked at an analyzed to determine if it is a
beneficial treatment option, with close examination on cancer specifically.
In order to perform immunology using T cells, there needs to be T cell receptor (TRC) is
this supposed to be TCR, instead of TRC? specificity against tumor antigens, along with the need
for the antigen-specific T cells to be activated and expansed typo- expanded . Any
immunosuppressive factors present must also be overcome in order for the cytokines and lytic
compounds to be delivered. Some cancers, such as melanoma and other virus-associated
malignancies, have tumor-specific T cells that can mediate cancer regression; however, most
tumor cells will evolve to escape immunity through evasion and the subversion of normal
immune responses, leaving the T cells and their fighting system without a way to fight back. To
combat this problem, new immunology efforts have begun looking at T cell modifications
through genetics and using adoptive cell transfer (ACT), which is the process of utilizing tumor

specific T cells an isolating them from the tumor-infiltrating lymphocytes where they are then
activated and expanded in vitro before being re-infused back into the patient.
In the research done at the Peter MacCallum Cancer Center in Melbourne, Australia with
Michael Kershaw, Jennifer Westwood, and Phillip Darcy, they have begun looking into the
process of ACT in order to determine its efficiency. In a tumor, its cells can express certain
molecules called tumor-associated antigens (TAAs). At times, T cells can respond to the TAAs,
but often are rendered unable to [the] dont think this belongs respond due to immune tolerance
from the tumors. [But] maybe another word other than this such as, yet, Im not sure on staring
sentences with but, genetic engineering can allow the T cell genes being encoded with surface
cell receptors that are able to detect the TAAs. These receptors are often derived from patients or
mice, and sometimes even chimeric antigen receptors (CARs), which are synthesized and
composed of extracellular TAA-specific antibodies. In order to achieve affinity of the TRC TCR
for the TAA to enhance the activity of the modified cells for immunotherapy, one option is to
change the amino acid composition of the antigen-binding regions (Darcy). In other trials done
under the Department of Medical Oncology in the UK, the TRC TCR beta chain has been
demonstrated to respond against the protein antigen targeted by the antibody. This showed that T
cells could respond independent of MHC-TRC TCR interaction maybe an explanation of what
MHC-TRC is (Gilham).
To begin testing the possibility of using T cell genetic engineering for immunotherapy,
there were various precautions needing to be taken initially before clinical trials began. Any
form of treatment has its dangers, but one that has not received much clearance before does not
have much intellect currently known in order to assess what potential hazards could be. In order

to ensure the safety of the process on patients, research had to be done on the T cells and the
insertion of the genetic modifications that would occur during the process. One such issue is
seen in retroviral gene transfer, which leads to higher levels of toxicity. There is little known
about the severity of the toxicity in particular cases, but there is protocol that helps to keep it
manageable. Often, the toxicity is due to the antibody targeted T cells where the tumor-specific
antigens are associated with the level of toxicity in the environment of the cells (Gilham). In
additional trials discussed in Michaela Sharpes and Natalie Mounts journal article on the
challenges and opportunities of T cell genetic modification, some of the biggest safety risks were
seen in on-target off-tumor activity, off-target reactivity, and cytokine-release syndromes. There
is the possibility of T cells triggering potent cellular responses against the tissues of the body,
which is known as on-target, off-tumor activity. In clinical trials, this has caused depletion of
normal B cells (Sharpe). As mentioned earlier, what is important? are important in the immune
system for the neutralization of pathogens. If the B cells are depleted, then the immune system
could be rendered helpless if the pathogens are no longer being neutralized and have no support
system for the T cells. Each process in the immune system has its purpose, and having the B
cells to recognize the antigen is critical so that the T cell can ultimately fight back. Through this
on-target, off-tumor activity, the challenges of identifying the tumor-specific targets is
highlighted, especially with the TCR T-cell therapies where the peptide target sequence being
present in other proteins (Sharpe).
Despite the safety risks associated with the T cell genetic modifications, there have been
multiple positives in the outcomes of many trials that have been conducted. In TRC clinical
trials performed at the Peter MacCallum Cancer Center discussed in the Nature Reviews journal,

human T cells were transduced with a gene isolated from patients with melanoma. Four of the
thirty-one patients demonstrated objective responses where evidence was provided that the T
cells could induce responses in patients to trigger further studies with improved gene-modified T
cells. In addition, CAR clinical trials were also performed that involved first-generation
receptors in ovarian cancer. Initially, there were no significant responses, but in a firstgeneration CAR targeting a particular peptide chain in patients with neuroblastoma, three out of
the nineteen patients had complete responses (Darcy).
As more clinical trials continue, the field of T cell therapies continues to see significant
clinical advances. The biggest advances are due to small findings as immunology and the
technologies involved becomes more improved and understood. As the identification of target
antigens is addressed and the persistence and ability of the T cells to exert the desired anti-tumor
effects are looked at, more therapies involving gene cell therapy can emerge. The new data
emerging does provide challenges as risks are exposed and the cost of such a therapy increases,
but the initiative can be adapted to the current situation for trials performed. It still seems too
soon to ultimately decide if our immune system is capable of fighting back, but maybe with a
little help, we can give it that little push in the right direction for the ultimate battle against
cancer.

Works Cited

Beginners Guide to T Cells T Cell Modulation Group. Institute of Infection and Immunity.
2009 Web. 30 March 2016
Darcy, Phillip K., Michael H. Kershaw, and Jennifer A. Westwood. Gene-engineered T Cells
for Cancer Therapy Nature Reviews: Cancer Volume 13 (August 2013): p. 525-541.
Web. 2 March 2016
Gilham, DE., RE Hawkins, W Mansoor, and FC Thistlewaite. Engineering T Cells for Cancer
Therapy British Journal of Cancer. Volume 93 (2005): p. 1085-1091. Web. 3 March
2016
Immune System National Institute of Allergy and Infectious Diseases. National Institutes of
Health. Jan. 2014 Web. 31 March 2016
Sharpe, Michaela and Natalie Mount. Genetically Modified T Cells in Cancer Therapy:
Opportunities and Challenges. The Company of Biologists. The Company of Biologists
Ltd (2015): p. 337-350. Web. 6 March 2016