By John Voudouris

For decades, scientists have been perplexed by the biological anomaly that is
cancer. Around 10 million people will die this year—and every year—from cancer
despite the numerous treatments that have been developed (Roser M. et al., 2015).
These treatments include surgery, hormone therapy, hundreds of different
chemotherapy drugs, radiation and much more. However, none of these solutions have
been perfectly effective in treating their intended cancers, with most having unintended
consequences including nausea, hair loss, physical deformation and even contribution
to future cancers. There must be a better way to treat cancer effectively with minimal
side effects. Immunotherapy may be the answer, but it must be considered whether
immunotherapy is, in its current state, worth pursuing as a cure to some cancers.
Scientists must ask themselves, what specific treatment can utilize the advanced
human immune system to combat cancer?

Scientists have determined that cancer cells are successful at disguising
themselves as normal cells by displaying regular antigens which prevents the immune
system from ultimately identifying and destroying them. What if scientists could induce
the immune system to identify cancerous cells and kill them almost instantly while still
preserving healthy cells? In essence, immunotherapy aims to identify cancerous cells
and make them evident to the immune system. One current example of immunotherapy
is monoclonal antibodies, which are a way of producing antibodies in a lab, using
eukaryotic cells, that stick to cancer cells and identify them to the killer cells.
Specifically, monoclonal antibodies are made by fusing a white blood cell (spleen cell) to
a cancer cell with the desired antibody. The fused cell, called a hybridoma, now
produces the desired antibody which can be injected into the body, sticking to the
antigen of the cancer cells (NCI, 2021). This is because the cancer cells will contain the target antigen and continue dividing, while the spleen cells will take the antigen and
produce an antibody.

This hybridoma is now “immortal” as well, as it divides
uncontrollably and will produce antibodies indefinitely. This is essentially an infinite
source of effective antibodies that can be used efficiently. Monoclonal antibodies can
also take a multifaceted approach to kill cancer cells. For example, blinatumomab binds
to the CD19 protein on leukemia cells and CD3 on T cells, which allows the killer cells to
first identify and then get close enough to the leukemia cells to destroy them. These are
known as polyclonal antibodies, which allow scientists to make multiple effective
antibodies in the same cell, saving time, resources and lives. In 1985, a group of
scientists tried to target numerous human tumor cells, using 3 monoclonal antibodies
with different target antigens. In summary, they found significant reactivity between the
tumors and the monoclonal antibodies, particularly with the breast carcinomas, but
equally with the other tumor cells. This test allowed scientists to understand that even
though some of these tumor cells contained similar proteins, the antibodies reacted
differently. Overall, this displayed the potential of monoclonal antibodies but also
displayed the necessity to ensure that the proper proteins are being targeted (Reeve et
al, 1985). More research is needed to determine which proteins are most effective to
target different cancers. Scientists believe that monoclonal antibody treatment can be
effective against a significant number of cancers, including some of the most common
and most deadly cancers. According to the Mayo Clinic, the following cancers can
potentially be treated using monoclonal antibodies, assuming that the cells display a
unique antigen (these cancers can display unique antigens):

● Brain cancer
● Breast cancer
● Chronic lymphocytic leukemia
● Colorectal cancer
● Head and neck cancers
● Hodgkin’s lymphoma
● Lung cancer
● Melanoma
● Non-Hodgkin’s lymphoma
● Stomach cancer

While monoclonal antibodies hold significant potential, the reality is that there are
many problems with this treatment. The most notable problem is that monoclonal
antibodies target one antigen, but cancer cells can produce surface proteins identical to
those found on most normal cells. If monoclonal antibody treatment was to be
conducted on these cells, the antibodies would stick to the proteins of the normal cells,
potentially contributing to a fatal scenario where the killer cells attack normal cells
(autoimmune issue). Let’s take an example of a monoclonal antibody treatment, named
rituximab, which binds to the protein CD20 on B cells and some types of cancer cells.
Unfortunately, one major issue that can be identified with this treatment is the side effect
of killing many B cells because they also have this protein. This can lead to the
suppression of the immune system and potentially expose the patient to infection during
treatment. Hence, monoclonal antibody treatment can only be utilized for cancer cells
with specific surface proteins, leading to the requirement of significant testing to
determine if a patient is protein “X” positive.

Similarly, scientists found that cancer cells can use epigenetic changes, which regulate the transcription rate of certain genes, to better relate to their local tissue and turn off genes present in cells from their original tissue. Cancer cells can therefore change their cell type, potentially rendering monoclonal antibody treatment ineffective against epigenetic changes (Elsevier, 2017).

In addition, Denovo Biotechnologies reported that approximately 99% of the cells from
their tests do not survive the fusion process of the cancer cell and the unique white
blood cell (Denovo Biotechnology, 2021). This is highly inefficient and contributes to the
already extremely high costs of this treatment. Another concern is the efficacy of this
treatment itself. Scientists have found that the fragment antigens in the hybridoma can
lead to slight discrepancies in the antibodies produced when used against the antigens
of the cancer cells. These discrepancies can lead to an inability for the antibodies to
recognize the original cancer antigen and become ineffective. Scientists are not sure
why this happens, but they hypothesize that there is some error in the translation of the antigen to the antibody in the hybridoma. In this case, the process would need to be
started all over again, wasting more money and more resources. Finally, it must be
noted that although monoclonal antibodies were first developed in 1975, they are still in
relatively early stages of major development, currently undergoing tests in mice and
rats, and not in humans.

While monoclonal antibodies hold the potential to become one of the most
effective forms of immunotherapy, they are still in early experimental applications that
require significant testing to become a viable cancer treatment in humans. Even so,
there are significant challenges with the high price and high fusion inefficiency of the
cells. Price is a significant inhibiting factor for many treatments around the world – in
both developed and developing nations – and monoclonal antibody treatment is no
exception. Additionally, there are challenges in recognizing the original antigen due to
discrepancies in accurately producing the antibodies. However, unlike the current
treatments, namely radiation therapy, monoclonal antibody treatment does not require
significant amounts of expensive equipment; primarily an intravenous delivery method.
In effect, monoclonal antibody treatment would be much more accessible to individuals
all around the world, even in locations with less advanced medical centers. It is my
opinion that monoclonal antibodies must be investigated and developed as a prime
immunotherapy treatment because of the practical and effective potential that it holds.
Scientists will likely find a way to make this treatment more affordable, more efficient
and just as effective in humans as shown in mice. Until then, more research is needed.

References:

Adenosine. (2021). Monoclonals.png – Wikimedia Commons.
https://commons.wikimedia.org/w/index.php?curid=9659630

Cancer.org (2021). Monoclonal Antibodies and Their Side Effects. Retrieved 6
August 2021, from
https://www.cancer.org/treatment/treatments-and-side-effects/treatment-types/immunoth
erapy/monoclonal-antibodies.html

Denovo Biotechnology. (2021). What are the advantages and disadvantages of
using Monoclonal antibodies Vs Polyclonal antibodies? Retrieved 6 August 2021, from
https://www.denovobiotech.com/support-center/article/2-what-are-the-advantages-and-d
isadvantages-of-using-monoclonal-antibodies-vs-polyclonal-antibodies

Elsevier. (2017). Cancer Cells Disguise Themselves by Switching Off Genes,
New Research Reveals. Retrieved 6 August 2021, from
https://www.elsevier.com/about/press-releases/research-and-journals/cancer-cells-disgu
ise-themselves-by-switching-off-genes,-new-research-reveals

Mayo Clinic (2021). Monoclonal antibody drugs for cancer: How they work.
Retrieved 8 September 2021, from
https://www.mayoclinic.org/diseases-conditions/cancer/in-depth/monoclonal-antibody/art
-20047808

National Cancer Institute (NCI). (2021). Monoclonal Antibodies. Retrieved 6
August 2021, from
https://www.cancer.gov/about-cancer/treatment/types/immunotherapy/monoclonal-antib
odies

Reeve, J.G., Wulfrank, D.A., Stewart, J., Twentyman, P.R., Baillie-Johnson, H.
and Bleehen, N.M. (1985), Monoclonal-antibody-defined human lung tumour
cell-surface antigens. Int. J. Cancer, 35: 769-775.
https://doi.org/10.1002/ijc.2910350612

Roser, M., & Ritchie, H. (2015). Cancer. Our World In Data. Retrieved from
https://ourworldindata.org/cancer