Tony Yang

7th Period
11/3/16
Independent Study: Track Hours

Source Number Letter: Source I

Citation: 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.
Source Validation: S
ource is published in the scientific journal Nature and written by
multiple PhD scientists. (I know its irrelevant but the second author is my moms old
boss!)
How did you find this source?: Through the use of Google Scholar
Intended audience: Other scientists studying in the field.
What arguments/topics does this source discuss?: A
rticle discusses CARs
(Chimeric Antigen Receptors) and their function in battling cancer. It then details the
structure of CAR and why it can be useful. The article then discusses the process of
applying gene therapy to t-cells through the use of genetic engineering. This CARs
would then be able to identify carcinogenic cells and enact an immune response from
the body. Finally, the article discusses the most effective current CAR designs and what
cancers they are effective at targeting
Minimum 3 quotes, paraphrases, summaries of source text that seem likely to be
helpful in future writing:
Most CARs consist of an antigen-recognizing single-chain antibody domain that is
connected to the trans-membrane and cytoplasmic tail by a stalk derived from a human
immunoglobulin Fc region, or CD8. The length of the stalk may influence the ability of the
CAR to bind to target antigens, depending on their conformation and accessibility, and it
may allow T cells to overcome steric hindrance and attain sufficient proximity to achieve
a cytotoxic reaction"
...list of T-cell populations that can be used for immunotherapy with CARs: bulk
peripheral blood mononuclear cells (PBMCs), CD8+ (CD4-depleted PBMCs), PBMCs
that are selectively depleted of T-regulatory cells (Tregs), isolated central memory T
(Tcm) cells, EpsteinBarr virus (EBV)-specific CTLs, and tri-virus-specific
CTLs.25,26,27,28 PBMCs ...cooperate for more effective immune responses

"CD19 is expressed at high levels on essentially all B-lineage leukemias and

lymphomas, including pre-B acute lymphoblastic leukemias (pre-B ALLs), chronic
lymphocytic leukemia (CLL), and lymphomas. Critically, CD19 is not expressed on
hematopoietic stem cells (or other tissues), so there should not be myelosuppressive
effects or other organ toxicities from targeting cells that express it.
Reflection

This source was about 18 pages in size 8 font and was filled scientific terms and text that
was confusing in some areas. The text contained lots of detailed information and made
use of many acronyms that I am unfamiliar with.
Source Number Letter: Source J
Citation: D
avila, 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.
Source Validation: S
ource is published in the scientific journal Nature and written by
multiple PhD scientists.
How did you find this source?: Through the use of Google Scholar
Intended audience: Other scientists studying in the field.
What arguments/topics does this source discuss?: T
his article discusses the
effectiveness of B-cells in targeting acute b-cell lymphoma. The article talks about how it
was done through the use of T-cells engineered with the CAR CD19 antigen. The source
then goes on to discuss the results. These results for the main part were highly
successful in patients with the Philadelphia Chromosome. The article discusses
different hypothesis of why this particular disease worked so well with the CAR
engineered T-cells. Finally, the article discusses what came out of this trial on humans
as the researchers are now able to make a roadmap for clinics considering the use of
T-cell therapy.
Minimum 3 quotes, paraphrases, summaries of source text that seem likely to be
helpful in future writing:
T cell therapy with tumor-targeted chimeric antigen receptor (CAR)modified T cells has
recently transitioned from the laboratory to the clinic and yielded outcomes that support
the tremendous potential of this approach to cancer therapy
CARs are artificial receptors that redirect antigen specificity, activate T cells, and further
enhance T cell function through their costimulatory component (4, 5). Three groups,
including our own, have reported objective tumor responses when infusing autologous T
cells genetically modified with CD19-targeted CARs into patients with chronic
lymphocytic leukemia (CLL) and other indolent non-Hodgkins lymphomas
CAR-engineered T cells can induce in some patients a clinical syndrome of fevers,
hypotension, hypoxia, and neurologic changes associated with marked elevations of
serum cytokines (1
3). This spectrum of clinical and laboratory findings has been termed
a CRS, which, given the anecdotal nature of this phenomenon, has remained largely
undefined

Reflection
This source was about 12 pages and gave information over the targeting of b-cell
lymphomas using gene therapy. The promising results show immunotherapy may lead to
many new breakthroughs. It took me about three hours to completely finish reading this

article and analyze its contents as it also contained many detailed diagrams that were
hard to understand..

Source Number Letter: Source K

Citation: Heczey, A., & Louis, C. U. (2013). Advances in chimeric antigen receptor
immunotherapy for neuroblastoma. Discovery medicine, 16(90), 287.
Source Validation: S
ource is published in the scientific journal Nature and written by
multiple PhD scientists.
How did you find this source?: Through the use of Google Scholar
Intended audience: Other scientists studying in the field.
What arguments/topics does this source discuss?: S
ource first goes over
background information about what neuroblastoma is and how it is presently treated.
Then, the article moves on to talk about how immunotherapy can be applied in this
context in order to fight off the type of cancer. The CAR antigens are used to help target
tumor associated antigens which then triggers an immune response so that your own
body can fight off the tumor by itself. Then the article discusses the results of the use of
immunotherapy for the neuroblastoma. These results are positive for the large majority
and very promising for future human trials and possible use as a standard treatment for
neuroblastoma one day in the future.
Minimum 3 quotes, paraphrases, summaries of source text that seem likely to be
helpful in future writing:
Neuroblastoma (NBL) is the most common extracranial pediatric solid tumor and has
heterogeneous biology and behavior. Patients with high-risk disease have poor
prognosis despite complex multimodal therapy; therefore, novel curative approaches are
needed.
Immunotherapy is a novel therapeutic approach that harnesses the inherent activity of
the immune system to control and eliminate malignant cells. One form of immunotherapy
uses chimeric antigen receptors (CAR) to target tumor-associated antigens. CARs are
derived from the antigen-binding domain of a monoclonal antibody (MAb) coupled with
the intracellular signaling portion of the T cell receptor.
Several approaches may further enhance anti-tumor activity and persistence of CAR
modified cells, and if these can be safely translated into the clinic, CAR-based
immunotherapy could become a viable adjunct or potential alternative to conventional
treatment options for patients with NBL"

Reflection

This article was 8 pages and detailed over the use of CAR based immunotherapy for
neuroblastoma. Like every other article that Ive read, it is filled with academic
vocabulary and acronyms that I have never heard of. This slows down the reading
process and makes it so that I have to spend significantly more time to read. Overall it
took me about two hours to read through this article.

Reflection
In doing independent research once again, I was of course the only person that worked on my
track work. I read three scholarly articles this time instead of four as the first two articles that I
read were considerably longer than usual. The articles were published by phD professors and
researchers in various scientific fields. The articles that I read through took me about eight
hours collectively to read through and analyze as a whole. For my eight track hours this time I
focused heavily in doing more research into the use of immunotherapy in treating cancer. To
start off, I learned considerably more about how immunotherapy works as a whole. This
technology essentially works by engineering t-cells, the body's natural immune cell for targeting
disease, and giving them the ability to recognize cancer cells. Normally your body is not able to
kill them due to the fact that cancer cells are able to disguise themselves as normal functioning
body cells. Although for my last 8 track hours I read about many of the same things, this time I
was able to delve more deeply into the application and results from human trials. Specifically I
read about many applications on lymphomas and neuroblastomas . All of the experiments that I
read about resulted in success and allowed for the patients to see significant success in relapse
of the disease. This occurred for most of the experiments and meant that great promise for even
more future research is on the horizon. I also learned a lot more about the obstacles that still
remain in the way of successfully allowing CAR assisted immunotherapy to work. One of the
biggest issues is the problem that comes from a process known as antigen escape. This
process works similarly to something which could be compared to as the natural selection of
antigens. Because CAR immunotherapy targets a specific antigen and due to the fact that
cancer mutates heavily resulting in great variation. It is possible that a specific antigen is
targeted and all carcinogenic cells with that antigen are killed, however other cancer cells
without that antigen are able to live. Not only that, there is the huge issue of specificity.
Sometimes the mutated t-cells are not designed correctly so the process is very costly and
expensive in order to achieve a desired result. I discussed with my mentor very heavily about
this topic as this is his main focus of research. He gave me a picture of the current state of
things concerning CAR immunotherapy and how the future looks. As of now many antigens
have already been established as very effective for destroying certain types of liquid
lymphomas. A battle of patent wars is ongoing as companies attempt to patent antigen designs.
I was able to accomplish this research in the comfort of my own house in front of my desktop
computer. All of the research that I did for these eight track hours came over the course of a two
week period as I analyzed and slowly read the articles very carefully. I chose to do independent
research as I felt that it was the best option that I had to accomplish my track work for capstone.

Not only that, I really didnt have another feasible option as a backup as there is no way I could
do product creation and internships are not available to me at the time.