Name : Voon Guan Zhong

IM-17-0405
Extended Essay

Extended Essay

Name : Voon Guan Zhong

NCUK Number : IM - 17 - 0405

May 2018

Title of extended essay :

Investigation of research on immunotherapy and the

comparison of immunotherapy with chemotherapy

Word Count : 2198

Extended essay submitted in partial fulfilment for the Research and

Communications Studies module on the IFP programme, INTO
Manchester

Introduction
Name : Voon Guan Zhong
IM-17-0405
Extended Essay

Cancer has been the focus of research by many scientist for a very long time, and the goal is to

find a cure for cancer. Although many different treatments are currently available

(chemotherapy, radiation therapy), these approaches to cancer treatment deals with the

cancerous cells that is present in the body currently and does not prevent the re-emergence of it

in the future. However, due to advancement in researches in the oncology field, the discovery of

immunotherapy has been revolutionary and has allowed the scientist to look into ways of

equipping the immune system to fight off cancer. Whereby, immunotherapy is described as a

treatment which edits the human immune system to defend the body from bacteria and viruses.

(Dimberu and Leonhardt , 2011) Due to the recent success and breakthroughs in research

which has shown promising results for the use of immunotherapy to treat cancer.

The aims of this review is to evaluate the future of immunotherapy as a treatment for cancer by

comparing it with chemotherapy. This essay will first outline the immunotherapy approaches that

is being used. It will then discuss the difficulties that has hindered the research and also the

approach towards tackling the problems. Lastly, it will conclude the findings that has been found

and make recommendations according to the findings.

The application of immunotherapy.

Amongst the the vast variety of immunotherapeutic approaches to cancer, cancer vaccines

alongside a few others has been one of most researched on due to the familiarity of the usage
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of cancer and also the endless potential of vaccines to completely eradicate cancerous cells

and also the prevention of the cancer cells from forming again. The traditional idea of a vaccine

is used as a preventive mechanism to protect against infectious diseases (i.e. hepatitis B and

smallpox vaccination) (NHS,2016)

The core mechanism of vaccines is to act on the adaptive immune system of the body ;

whereby it aims to present the antigen that is on the cancer cell to the immune system to trigger

an immune response. The immune response then triggers the immune system to produce

memory-T cells that remembers the antigen and when the same antigen is present in the body,

it can be eradicated at a much quicker rate. (Snook and Waldman, 2013) However, vaccinations

relies heavily on professional antigen-presenting cells (APC) like dendritic cells (DC cells ) to

present the antigens to the T-cells to trigger the production of memory T-cells. Which is a

reason why scientist has looked into developing DC specific vaccines to increase the efficacy of

the vaccines. (Farkona , Diamandis and Blasutig, 2016)

Other than vaccines discussed above, immune-checkpoint blockade has also become the point

of interest of many scientist as it tackles one of the major problems that is present when treating

cancer which is the down-regulation of the immune system by the cancer cells. (Emens, et al. ,

2016) It can be further defined as the mechanism activated by the tumour cells to avoid and

evade the attack by the immune system. (Pardoll , 2012) Other than preventing immunity the

tumour cells can also be induce the body to have tolerance for the tumour cells. Consequently,

many professionals of the biomedical field are looking into developing agents which prevents

the cancer cells from activating this mechanism. An example of this mechanism in use is shown

by the application of the drug ‘Ipilimumab’ for the treatment of melanoma. The incentive of this

drug is to act as a an anti-CTLA 4 to help the immune system activate the its anticancer

mechanism. CTLA 4 is the inhibitory binding site of the anticancer T-cells that can diminish its
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effect to kill the tumour cells. The effect of the drug ‘Ipilimumab’ is to prevent the ligands

secreted by tumour to bind to inhibitory site, this usage of immune checkpoint blockade has

been approved by the Food and Drug Administration (FDA) of the United States as a treatment

for metastatic melanoma. (Farkona, Diamandis and Blasutig ,2016)

Challenges of immunotherapy

As stated above, the application and the usage of vaccine in the medical field has been

employed for an extensive amounts of time. In spite of this, there are still obstacles and

difficulties associated with implementing cancer vaccines : recognizing the most suitable antigen

to be used to make up the vaccine and also the lack of a efficient drug delivery system. (Snook

and Waldman, 2013) The antigen that can be used to develop cancer vaccines can be

generalized into two groups, Tumour-Associating Antigen (TAA) or Tumour-Specific Antigen

(TSA). Tumour-Specific Antigens are identified as antigen which specified to one type of tumour

and Tumour-Associating Antigen would be using a common antigen that is present on most

tumour. (Ye , 2018)

Both of these has their own drawbacks associated with it, one of the major concern with using

TAAs for vaccines is that the antigens found on the tumour can also be commonly found on the

normal cells of the body. The effect of this would be, the immune system would not elicit an

immune response against these type of antigen due to it being recognise as the body’s own cell

or in other words ‘self’ antigen. On the other hand, TSA presents a different type obstacle, that

is the antigen that is specified to each tumour is extremely scarce and therefore making it

difficult to find and locate it. (Ye , 2018)

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As for the immune checkpoint blockade, it was found by multiple research that side effects and

toxicity still poses as a threat to the patients when clinical trials was done. One of the side effect

of immune checkpoint blockade is the development of autoimmune disease ; defined as the

over-sensitivity of immune system to which it attacks its own body cells. (Wraith, 2017 ) Other

than scientific challenges, clinical difficulties to assess response of patients also makes it

difficult to for the clinical trials to have a accurate results. (Farkona , Diamandis and Blasutig ,

2016) The reason for this is because, unlike conventional cancer treatments like chemotherapy

which targets and kills the cancer cells which is evident through the rapid decrease in tumour

size. Immunotherapy generally works on a slower pace, and the signs of showing response may

take up to several months to make up and show a response. The time taken for the treatment to

work not only hinders the process of the treatment it also increases the risk for complications to

occur. (Ahn , Pillack and Okado . 2013)

Research that helped overcome obstacles

Nevertheless, despite the difficulties that has impede the implementation of immunotherapy as a

cancer treatment ; many advancements like the use of nanotechnology to enhance delivery

system of vaccines has given realistic hope to researchers and will trigger a greater initiative to

look for ways to help make cancer immunotherapy a reality. One of the most significant finding

that has helped overcome some of the obstacles, is the usage of nanotechnology in the medical

field and in particular, the drug delivery systems. One of the major problems as for cancer

vaccines as stated above is the difficulty in effectively delivering and presenting the antigens of

the vaccine to the immune system.(Snook and Waldman, 2013) The way that the nanoparticles

have an advantage over the conventional tactic of vaccine is that, nanoparticles has the

advantage of being minute particles that is able to penetrate through to the lymphoid tissues, of

which is the core of the immune system. Moreover, in spite of being extremely small, they have
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the ability to act as multifunctional nanoparticles which is meant by the ability to have a few

different components that have different functions. (Fan and Moon , 2015)

The characteristics of the multifunctional nanoparticles are the ability to deliver antigens to

antigen presenting cells stably, carrying adjuvants simultaneously to the antigen , achieving

highly specific and selective delivery, lastly, the ability to act as artificial antigen presenting cells.

These characteristics not only helped scientist to overcome the trouble of delivering the antigen

to the antigen presenting cells of the immune system. The ability to act as an artificial APC has

avoided the need to going through the process of delivery and presentation of the antigen. On

the plus side of obviating the process of using the natural APC may also have an added

advantage of avoiding the tumour cells from activating immune checkpoint molecules. (Fan and

Moon , 2015)

Comparison with chemotherapy

Conventional cancer treatments like chemotherapy has been used as a treatment for cancer for

a long time, however, there are a few major downsides for using chemotherapy and

immunotherapy may be able to avoid these downsides of chemotherapy. Nevertheless, there

are still advantages and disadvantages to both chemotherapy and immunotherapy, and the

comparison between them can be made around a few different points : side effects, cost, long-

term effects, and advantage of each treatment. The side effects of chemotherapy are commonly

known and can be evident to the naked eye, these side effects are hair loss, nauseous and loss
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of appetite. This is because chemotherapy kills the healthy cells when it is targeting the

cancerous cell. On the other hand, the over-toxicity is one of the most worrying side effect of

immunotherapy because if it is not handled properly, autoimmune disease may occur. The other

factor to consider is the cost of the treatment, the cost for immunotherapy is extremely high and

the sustainability of the the treatment is often questioned. An example for the high cost of

immunotherapy is the use of the ‘Ipilimum’ drug, whereby it costs around $30000 for an injection

and a treatment normally consist of 4 doses which adds up to $120000. (Fellner, 2012)

Chemotherapy however, have the average cost of around $7000 while it differs for different

types of cancer. Lastly, chemotherapy have the ability to quickly eradicate cancer cells and

target dividing tumour cells quickly but this effect can only last as long as the treatment last, and

this allows for the re-emergence of the cancer cells as the body is not geared or prepare to

counter a secondary attack from the cancer cells. One of the biggest promise of immunotherapy

is that that immune system of the body is able to deal with the cancer cells on its own without

any additional treatment, and it can have a more tumour-specific treatment than chemotherapy.

However, this comes with a price that is the treatment will take a longer time to work effectively.

Discussion

Immunotherapy has provided an alternative cancer treatment to chemotherapy which may been

seen as more advantageous ; however it still possesses its own limitation and side effects and

much more research still needs to be done for immunotherapy to become a viable cancer

treatment. This essay has investigated the research that has been done on the

immunotherapeutic approaches towards cancer treatment whilst comparing its advantages and

disadvantages towards conventional cancer treatment like chemotherapy that is widely used

around the world currently. Through investigation it has been found that although the potential of

immunotherapy is endless, many more challenges still need to be dealt with in order to make
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immunotherapy a mainstream cancer treatment. Other than that, it has also been found through

the comparison of immunotherapy with chemotherapy, that immunotherapy has some profound

advantage over chemotherapy whereby the effect of the treatment can prevent re-emergence of

the cancer and also have a highly specific treatment that can target the tumour specifically. On

the other hand, immunotherapy have many disadvantages regarding the time for treatment to

work and the cost of treatment. However, one of the most worrying factor about immunotherapy

is the fact that the autoimmune disease may arise from the treatment. This however, has been

found that in some cases that it can be controlled and managed without much difficulty.

Additionally, it is also know that the treatment differs from one person to another, the effect and

side effects that has affects one individual will not necessarily affect the other, thus, this has it

much more difficult to assess if the treatment is feasible and effective to treat cancer. Farkona,

Diamandis and Blasutig (2016) has stated that through the success of immunotherapy, many

other different kinds of treatment can go hand in hand with it to produce a better result. Snook

and Walkman (2014) has also agreed with this and state that the key for the transition of

immunotherapy to become a mainstream cancer treatment, is the knowledge of all the different

immunotherapeutic approaches and the knowledge of utilizing them together to produce the

best effect. Finally, Wraith (2017) recognizes that the future of immunotherapy is to be able to

treat the cancer without the side effect of autoimmune disease and the key factor is to

investigate the antigens in the immune system and the tumour.

Conclusion

To conclude, immunotherapy has been widely recognized as the future of cancer treatment,

with the potential of finally finding a cure for cancer. It also has proven to have quite a few

advantage over conventional treatment like chemotherapy. However, many obstacles lies
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between the path of making immunotherapy a success. Nevertheless, it is important to know

that progress is being made and it is only a matter of time before immunotherapy becomes a

mainstream cancer treatment. More effort should be put towards learning how immunotherapy

can affect the result of other treatments, as the knowledge of this is helpful for making other

treatments more effective. Studies should also be done on the usage of immunotherapy on

treatments other than cancer, this is because the immune system is closely related to most of

the disease and with enough knowledge these can be cured with ease as well.

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