New Treatments for CANCER ?

by Audrey Lai

Introduction

Nearly 10 million people die from cancer every year, making it the second most common cause of death in the world.1 Chemotherapy, radiation therapy, and surgery have been the traditional treatments for cancer since the 20th century and are still commonly used today. However, as many already know, the effectiveness of these traditional cancer treatments is often limited. Thanks to the quick development of technologies and medical discoveries, there are currently new, promising methods for treating cancer which includes immunotherapy, a modern medical innovation. In this article, we will explore what cancer is, how traditional cancer treatments work, and why we need immunotherapy, such as monoclonal antibodies and CAR T-cell therapy. First of all, what is cancer?

Cancer

Cancer is a non-communicable disease in which body cells grow and divide uncontrollably, spreading to other parts of the body via the bloodstream. Human body cells undergo mitosis, also known as cell division, in order to grow and repair old, damaged cells. A mutation in the gene that regulates a cell’s functions and division results in cancer. Genes involved in regular cell growth can become oncogenes or healthy tumour suppressor genes can become inactive as a result of a change in the DNA. Consequently, this mutation will cause uncontrolled cell growth. Gene mutations can result from random errors during cell division, damage to DNA caused by carcinogens such as tobacco, or inheritance from one’s parents. Cancer cells that have detached from their primary tumour and travelled through the bloodstream to form secondary tumours in other parts of the body are said to have metastasized.

Traditional Treatments

Surgery, chemotherapy, and radiation have always been popular options in treating cancer, yet the chances of a patient with cancer dying of it are similar to those of 50 years ago.2 First, chemotherapy works by using chemicals to shrink tumours, destroy or kill cancer cells, and help other treatments work better. However, the main drawback of chemotherapy is that it simultaneously kills cancer and healthy cells that grow and divide quickly, such as hair, skin, blood and intestinal cells. As a result, it leads to potential side effects like hair loss, nausea, fatigue, and infections. Second, radiation therapy works by using radiation to shrink tumours and slow the growth of cancer cells by damaging their DNA. It is a local treatment and can be given externally or internally. The disadvantages include damaging surrounding healthy cells, leading to side effects and patients also have a lifetime dose limit to the amount of radiation that can be received by the body. Third, surgery is another option for removing tumours grown from cancer cells. A limitation of surgery is that blood cancer or metastatic cancer that has spread cannot be treated with surgery. This makes surgery only available for removing solid, local tumours in the body. Therefore, targeted therapy like immunotherapy is designed to treat targeted cancer cells.

Immunotherapy

The immune system helps detect and destroy any foreign or abnormal cells in our body including cancer cells. Immunotherapy is a type of cancer treatment, which aims to encourage the patient’s immune system to target cancer cells and destroy them. The treatments are designed to target a specific antigen on a specific type of cancer cell while sparing healthy body cells. Immunotherapy includes cancer vaccines, adoptive cell therapy (CAR T-cell therapy), checkpoint inhibitors and monoclonal antibodies. Over 100 different types of cancer exist today, which is a significant number. 3Therefore, since each type of cancer can be significantly distinct, a more targeted and focused approach is needed.

Monoclonal Antibodies

One of the popular methods of immunotherapy is monoclonal antibodies. Did you know that the EU and the US have approved around 100 therapeutics monoclonal antibodies for treating both cancer and non-cancer diseases? 4Monoclonal antibodies are becoming more and more common in the field of medicine due to their ability to bind to a specific protein or antigen on cell membranes. Other applications of monoclonal antibodies include the delivery of medications to cancer cells, the attachment of fluorescent substances to detect specific cells, pregnancy testings, and the diagnosis of numerous diseases such as HIV.

How are monoclonal antibodies produced?5

1. A type of antigen on the cancer cell is injected into mice and their B-cell lymphocytes are stimulated to produce the antibodies for the specific antigen.

2. The mice undergo blood screening for the antibody production.

3. The splenocytes which produce the B-lymphocytes are removed.

4. The splenocytes are fused with myeloma cells, which can divide unlimitedly, forming hybridoma cells.

5. The hybridoma cells divide and produce many clones specific to cancer’s antigen.

6. The clones are screened and selected, then purified. As a result many clones of antibodies are made.

How do monoclonal antibodies work in the body?

1. Monoclonal antibodies are injected into the patient’s bloodstream.

2. They will locate proteins called antigens on cancer cells.

3. Since the monoclonal antibodies are specific to the antigen on cancer cells they will bind and form an antibody-antigen complex.

4. The antibody will then signal other immune cells.

5. The immune cells will arrive and help destroy cancer cells.

Monoclonal antibodies treatment in cancer:

In recent years, monoclonal antibodies have become an option for treating cancers. An example is rituximab (Rituxan), a monoclonal antibody targeting leukaemia and B-Cell non-Hodgkin lymphoma (NHL). According to a study, patients with lymphomas who received rituximab and chemotherapy had a better survival rate than those receiving chemotherapy.6

Car T-Cell Therapy

Did you know since 2017, six CAR T-cell therapies have been approved by the FDA for the treatment of blood cancers? 7Acute lymphocytic leukaemia has a 40% 5-year survival rate for people aged 20 and older.8 However, blood cancer is now incredibly manageable due to decades of research and the introduction of innovative treatments like CAR T-Cell therapy.

How are CAR T-cells made:

1. Blood is drawn from a patient which moves through a blood separator to collect the T-cells, the remaining blood components will return to the blood.

2. The T-cells are genetically engineered by editing their gene to produce a protein on their surface (chimeric antigen receptors) which bind to specific proteins or antigens on the cancer cells.

3. Genetically modified T-cells are grown until there are millions of them and then they are collected.

How CAR T-cells work in the body:

1. After producing the CAR T-cells, they are reinfused back into the patient’s blood.

2. In the body, the CAR T-cells will bind to proteins on the cancer cells.

3. This will signal the immune system to destroy them.

CAR T-cell therapy treatment in cancer: tisagenlecleucel is a CAR T-cell medication to treat B-cell acute lymphoblastic leukaemia. In 2021, a patient in Hong Kong was successfully treated with tisagenlecleucel (Kymriah). 9After relapsing twice from chemotherapy and haematopoietic stem cell transplantation, he was recommended CAR-T cell therapy. After the treatment, he recovered without experiencing any serious complications and results from bone marrow examinations show that no leukaemia cells could be found.

Modern VS Traditional

On one hand, immunotherapy seems to be a modern, better treatment due to its capability to target particular cancer cells while sparing healthy cells. This makes patients receiving targeted therapy experience fewer and less severe side effects compared to chemotherapy. However, there are a lot of drawbacks to the treatment. Decades of study, several pharmacological trials, and substantial financial resources are needed to develop a drug. Hence, immunotherapy is quite costly and out of reach for many individuals. For example, targeted therapy drugs like trastuzumab (Herceptin) for breast cancer costs $500,000 HKD per year and sorafenib (Nexavar) for liver cancer costs $150,000 HKD per month.10 This raises ethical issues because it is unfair that only wealthy people are able to access the latest advanced treatments for cancer. Conversely, there are also some highly effective traditional treatments even when they cannot specifically target cancer cells. In order to reduce costs and give all citizens an equal chance to obtain cancer treatment, a possibility is for the government to invest more in subsidising cancer treatment research. To conclude, both traditional and immunotherapy treatments for cancer could be used.

Bibliography

[1] WHO International Agency for Research on Cancer. “WHO International Agency for Research on Cancer.” “Cancer Today.” Published 2020. Global Cancer Observatory, https://gco.iarc.fr/today/online-analysis-pie?v=2020&mode=population&mode_population=income&population=900&populations=900&key=total&sex=0&cancer=39&type=1&statistic=5&prevalence=0&population_group=0&ages_ group%5B%5D=17&nb_items=7&group_cancer=1&include_nmsc=1&include_nmsc_other=1&half_pie=0&donut=0.

[2] Goodman, Amy, et al. “Why the ‘Slash-Poison-Burn’ Approach to Cancer Has Failed.” Truthout, Truthout, 23 Dec. 2019, https://truthout. org/video/why-the-slash-poison-burn-approach-to-cancer-has-failed/.

[3] “What Is Cancer?” National Cancer Institute, https://www.cancer.gov/about-cancer/understanding/what-is-cancer#:~:text=There%20 are%20more%20than%20100,cancer%20starts%20in%20the%20brain.

[4] “UpToDate.” Www.uptodate.com, www.uptodate.com/contents/overview-of-therapeutic-monoclonal-antibodies/print#:~:text=Since%20 1985%2C%20approximately%20100%20monoclonal.

[5] “Monoclonal Antibody Production.” Molecular Devices, https://www.moleculardevices.com/applications/monoclonal-antibody-production#gref.

[6] Schulz, Holger, et al. “Chemotherapy plus Rituximab versus Chemotherapy Alone for B-Cell Non-Hodgkin’s Lymphoma.” Cochrane Database of Systematic Reviews, vol. 2010, no. 1, 17 Oct. 2007, www.ncbi.nlm.nih.gov/pmc/articles/PMC9017066/, 10.1002/14651858.cd003805.pub2.

[7] “Car T Cells: Engineering Immune Cells to Treat Cancer.” National Cancer Institute, https://www.cancer.gov/about-cancer/treatment/research/car-t-cells#:~:text=Since%202017%2C%20six%20CAR%20T,%2C%20most%20recently%2C%20multiple%20myeloma.

[8] “Leukemia - Acute Lymphocytic - ALL - Statistics.” Cancer.net, 25 June 2012, www.cancer.net/cancer-types/leukemia-acute-lymphocytic-all/ statistics#:~:text=The%205%2Dyear%20survival%20rate%20for%20people%20age%2020%20and.

[9] “HKUMED Introduces Hong Kong’s First Car-T Cell Therapy for Blood Cancer Patients.” HKU Li Ka Shing Faculty of Medicine, 10 Feb. 2021, https://www.med.hku.hk/en/news/press/20210210-hk-first-car-t-cell-therapy-for-blood-cancer-patients.

[10] “Targeted Therapy Drug: Cancer Treatment, Cost & Funding in Hong Kong.” Www.cigna.com.hk, www.cigna.com.hk/en/smarthealth/medical/targeted-therapy-drug-cancer-treatment-cost-funding-in-hong-kong.