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Tony Yang
Mrs. Greene
Capstone- 7th Period
1 November 2016
CAR T-cell Therapy
Cancer has been present in human society since the dawn of our existence. A dynamic and ever
changing disease, its randomness and enigmatic nature makes it a truly challenging task for
todays researchers. However, with recent biological advancements into understanding the
disease, new treatments concepts have been created. One such process can be seen in the rapidly
developing treatment known as cancer immunotherapy. Cancer immunotherapy, through the use
of a process called CAR (Chimeric Antigen Receptor) T-cell therapy, is an innovative approach
to curing many different types of cancers that is effective in both specificity and pain. While
many drawbacks still exist with the technology, continued research into immunotherapy could
act as a promising and effective way to treat and cure cancer in the near future through the use of
the bodys own cells.
T-cell therapy is a process that utilizes many 21st century biotech advancements to
function as way to cure cancer. Through the late 1900s into the present era, developments like
electron microscopes and better research methods have given scientists a better understanding of
both the human immune system and cancer cells. A large portion of the immune system function
is based off of a special group of cells known as T-cells. T cells mature in the thymus... express
TCR (T cell receptor), and can express either CD8 glycoprotein on their surface and are called
CD8+ T cells (cytotoxic) or CD4 glycoprotein and are then called CD4 cells (helper T cells)
(Golubovskaya). These T-cells use molecules called antigens to differentiate between different

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things inside of the body. In CAR T-cell therapy, artificial T-cell receptors that can bind to
specific antigens are engineered into T-cells. These CARs are derived from the antigen-binding
domain of a monoclonal antibody coupled with the intracellular signaling portion of the T cell
receptor (Kohn). The artificially made CARs can then be used to target specific antigens on
cancer cells as cancer cells hold distinct differences in their expressed antigens. While cancer
cells are normally able to escape detection through various methods like disguising themselves
as normal body cells, CARs will essentially allow for differentiation between normal and
cancerous cells, subsequently leading to an immune response.
In actual experiments on humans, CAR T-Cell Therapy has shown great promise in
studies done so far as more focus is being put into testing its viability. Very generally speaking, it
has already been shown that T cell therapy with tumor-targeted chimeric antigen receptor
(CAR)modified T cells has... yielded outcomes that support the tremendous potential of this
approach to cancer therapy (Davila). However despite the fact that success has been shown, due
to every type of cancer being different and unique in its own way, CAR T-cell immunotherapy
has shown greater efficacy in certain tumors. Particularly convincing results have been seen with
neuroblastoma as a potential alternative to conventional treatment options (Onea), and B-cell
lymphomas. The results of CAR targeted treatment have shown to result in partial or complete
remissions in... patients with advanced disease, with no persistent toxicities (Onea). The
advantage of using this treatment is it equips the body to fight cancer like a virus or bacteria,
rather than killing everything in a targeted area as with chemo and radiation therapy. While these
two conventional cancer treatments also work, their ability to kill cancer cells also means that
they will more than likely destroy normal healthy body cells as well. CAR T-cell therapy on the
other hand has the ability to target cancer cells specifically, which subsequently leaves normal

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cells alone. This is revolutionary in that patients can leave treatment without the feeling of pain
or extreme sickness, and for that reason should have more research and funding to allow for
rapid development of the treatment.
At the same time however, many prevalent drawbacks still exist in preventing CAR Tcell therapy from being utilized today. Firstly, much of the success in using CAR t-cell therapy
has come from use on liquid tumors like leukemia. For an unknown reason that scientists have
not been able to pinpoint, CARs are still not able to effectively work on solid tumors however
many hypothesis have yet to be tested (Golubovskaya). Also, there is a problem commonly
called antigen escape. Due to how CAR T-cell therapy exerts selective pressure on tumor cells,
it will result in the development of new genetic variants that evade treatment (Golubovskaya).
Essentially what is happening is the natural selection of cancer cells. Due to the fact that CARs
target specific antigens and that each tumor is constantly mutating and thus may express different
antigens, it is possible for the engineered t-cells to be unable to kill all of the tumor mass.
Finally, due to an increased amount of T-cells being present, CAR therapy can cause prolonged
toxicities because the engineered T-cells can persist in the body even after treatment is no longer
required (Golubovskaya). This is a problem in that prolonged exposure to cytokines can
potentially result in a cytokine storm, a potentially fatal chain reaction due to a positive feedback
loop in the immune system. With the presence of all of these drawbacks, the only way to solve
them is through the use of increased research. With the great potential that exists for CAR T-cell
therapy, it is only logical that we allocate more resources so that development can be accelerated.
With the advent of modern technology and research methods, scientists are able to think
creatively and come up with new innovations. As a result, new methods of solving problems
have been created with only more to come. Using CARs to target cancer cells is an intuitive way

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to utilize ones own immune system to fight cancer in a painless and effective way. Despite the
many drawbacks that still exist with this treatment method, through the use of more research and
funding, CARs can eventually be developed into an effective treatment to treat and prevent
cancer.

Works Cited
Davila, M. L., Riviere, I., Wang, X., Bartido, S., Park, J., Curran, K., ... & Qu, J. (2014). Efficacy
and toxicity management of 19-28z CAR T cell therapy in B cell acute lymphoblastic
leukemia. Science translational medicine, 6(224), 224ra25-224ra25.
Golubovskaya, V., & Wu, L. (2016). Different Subsets of T Cells, Memory, Effector Functions, and
CAR-T Immunotherapy. Cancers, 8(3), 36.

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Kohn, D. B., Dotti, G., Brentjens, R., Savoldo, B., Jensen, M., Cooper, L. J., ... & Heslop, H. E.
(2011). CARs on track in the clinic. Molecular therapy,19(3), 432-438.
Onea, A. S., & Jazirehi, A. R. (2016). CD19 chimeric antigen receptor (CD19 CAR)-redirected
adoptive T-cell immunotherapy for the treatment of relapsed or refractory B-cell NonHodgkins Lymphomas. American journal of cancer research, 6(2), 403.