John Voudouris, Upper Canada College, Toronto, Ontario, Canada
For decades, scientists have been perplexed by one of the world's most common diseases: cancer. Around ten million people die annually from cancer despite the numerous treatments that exist, including surgery, hormone therapy, chemotherapy drugs, and radiation (Roser M. et al, 2015). None of these treatments have been 100% effective in treating the targeted cancers, with most causing unintended side effects, such as nausea, hair loss, physical deformation, and even increased risk for future cancers.
There must be a more effective way to treat cancer with minimal side effects. Immunotherapy may be the solution, but whether current cancer immunotherapies are worth pursuing is important to consider.
Scientists have determined that cancer cells disguise themselves as normal cells by releasing antigens, which prevent the immune system from identifying and destroying them. Chemotherapy, as an example, frequently relies on killing all rapidly dividing cells. While this might effectively kill cancer cells, it also kills healthy cells in the hair, skin and nails.
Yet, what if scientists could find a way to make the immune system identify and kill cancerous cells while still preserving healthy cells? In essence, this is what immunotherapy aims to do. One example of immunotherapy is the use of monoclonal antibodies, which are created in laboratories using eukaryotic cells to identify cancer cells. Monoclonal antibodies are made by fusing a white blood cell (spleen cell) to a cancer cell. This forms a cell called a hybridoma that produces the desired antibody, which can be injected into the body to stick to the antigen of the cancer. The white blood cell will create the antibody while the cancer cell will divide uncontrollably and contain the target antigen. This hybridoma is considered “immortal'', since it divides uncontrollably and will produce antibodies indefinitely (NCI, 2021).
Monoclonal antibodies can also take a multifaceted approach to kill cancer cells. For example, blinatumomab, a monoclonal antibody drug, binds to the CD19 protein on leukemia cells and CD3 protein on T cells, which allows the killer cells to first identify and then get close enough to the leukemia cells to destroy them (NCI, 2021). These are known as polyclonal antibodies, which allow scientists to make multiple effective antibodies in the same cell, saving time, resources, and lives. In summary, 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. However, more research is needed to determine which proteins are most effective to target specific cancers. According to the Mayo Clinic, the following cancers can potentially be treated using monoclonal antibodies, assuming that the cells display a unique protein on their surface (Mayo Clinic, 2021):
Brain cancer
Breast cancer
Chronic lymphocytic leukemia
Colorectal cancer
Head and neck cancers
Hodgkin's lymphoma
Lung cancer
Melanoma
Non-Hodgkin's lymphoma
Prostate cancer
Stomach cancer
While it is clear that monoclonal antibodies hold significant potential, there are still many problems with this treatment. The most notable issue is that monoclonal antibodies only target one antigen, but cancer cells can produce surface proteins identical to those found on most normal cells (Elsevier, 2017). If monoclonal antibody treatment was conducted on these cells, the antibodies would stick to the proteins of the normal cells, potentially causing the killer cells to fatally attack normal cells (autoimmune response). An example of a monoclonal antibody treatment, named rituximab, binds to the protein CD20 on B cells and some types of cancer cells. Unfortunately, one major issue with this treatment is its side effect of killing many B cells because they also have this protein. This can lead to the suppression of the immune system, which potentially exposes the patient to infection during treatment (University of Pennsylvania, 2021). Hence, monoclonal antibody treatment can only be utilized for cancer cells with specific surface proteins, requiring significant testing to determine if a patient can even benefit from immunotherapy treatment.
Similarly, scientists found that cancer cells can change their cell type, potentially rendering monoclonal antibody treatment ineffective against epigenetic changes (Elsevier, 2017). Through epigenetic changes, which regulate the transcription rate of certain genes, cancer cells are able to turn off genes present in cells from their original tissue. Additionally, 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, drastically increasing the already high costs of this treatment (Denovo Biotechnology, 2021).
Another concern is the efficacy of the treatment itself. Scientists have found that the small peptide and fragment antigens in the hybridoma can lead to discrepancies in the antibodies produced when used against the antigens of the cancer cells (Denovo Biotechnology, 2021). These discrepancies render the antibodies as ineffective because they are unable to recognize the original cancer antigen. 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 repeated from the beginning, wasting more money and more resources. Lastly, although monoclonal antibodies were first developed in 1975, they are still in the early stages of development and have yet to be tested in humans.
Nonetheless, monoclonal antibodies would be a more cost-effective solution. Indeed, 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. However, unlike the current treatments, such as radiation therapy, monoclonal antibody treatment does not require expensive equipment but only 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.
In summary, while monoclonal antibodies hold the potential to become one of the most effective forms of immunotherapy, they require significant testing to become a viable cancer treatment in humans. Monoclonal antibodies should be investigated and developed as a prime immunotherapy treatment because of the practical and effective potential that they hold. Scientists will likely find a way to make this treatment more affordable, more efficient, and just as effective in humans as shown in mice models. Despite the current limitations, we will likely see monoclonal antibody therapy become a prominent treatment in the near future with the diligence of the upcoming generation of scientists.
References
Cancer.org (2021). Monoclonal Antibodies and Their Side Effects. Retrieved from https://www.cancer.org/treatment/treatments-and-side-effects/treatment-types/immunotherapy/monoclonal-antibodies.html
Denovo Biotechnology. (2021). What are the advantages and disadvantages of using Monoclonal antibodies Vs Polyclonal antibodies? Retrieved from https://www.denovobiotech.com/support-center/article/2-what-are-the-advantages-and-disadvantages-of-using-monoclonal-antibodies-vs-polyclonal-antibodies
Elsevier. (2017). Cancer Cells Disguise Themselves by Switching Off Genes, New Research Reveals. Retrieved from https://www.elsevier.com/about/press-releases/research-and-journals/cancer-cells-disguise-themselves-by-switching-off-genes,-new-research-reveals
Mayo Clinic (2021). Monoclonal antibody drugs for cancer: How they work. Retrieved from https://www.mayoclinic.org/diseases-conditions/cancer/in-depth/monoclonal-antibody/art-20047808
National Cancer Institute (NCI). (2021). Blinatumomab Effective for Children with Relapsed Leukemia. Retrieved from https://www.cancer.gov/news-events/cancer-currents-blog/2021/blinatumomab-relapsed-b-cell-leukemia-children-young-adults
National Cancer Institute (NCI). (2021). Monoclonal Antibodies. Retrieved from https://www.cancer.gov/about-cancer/treatment/types/immunotherapy/monoclonal-antibodies
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
University of Pennsylvania (OncoLink). (2021). Rituximab (Rituxan®). Retrieved from https://www.oncolink.org/cancer-treatment/oncolink-rx/rituximab-rituxan-r#:~:text=Rituximab%20is%20directed%20against%20a,attack%20and%20destroy%20those%20cells.