Cancer vaccination: Hope or Hype?

As various countries roll out the few COVID-19 vaccines that have been approved, many scientists, world leaders, and citizens hope that this will be a large step towards normalcy. Between report of efficacy data, mutant strains, and vaccine nationalism it is easy to overlook the effect the pandemic has had on cancer patients and their treatment.

More than 1000 patients in London needing urgent cancer surgery do not have a date for their treatment. With the knowledge that a four-week delay in treatment can increase mortality up to 8% it presents a significant risk to these patients1.

Treatment of cancer has centred around three main avenues of approach, including surgery, that have been used for decades. Although these treatment options are effective, some believe that they are outdated. So, what is next for cancer therapy?

Our understanding of the immune system, and how it is manipulated to tolerate cancerous cells, could help researchers to develop immunotherapies, such as cancer vaccines.

Slash, Burn, and Poison: Effective?

The three main treatment options of cancer centre around the destruction of cancer cells within the body. The approaches (Figure 1)2, slash, to represent surgical removal of tumors, burn, to represent the use of radiation to kill cancer cells, and poison, to represent chemotherapy has been utilised to treat, and even cure cancer.

Figure 1: The three main approaches to treat and even cure cancer include slash, burn, and poison which can cause a wide range of side-effects for the patient.

However, some academics and clinicians such as Dr Azra Raza, believe this approach is out-dated given the fact radio and chemotherapy causes a wide range of debilitating side-effects. A study into the side-effects of chemotherapy presented that 86% of patients reported at least one side-effect, that ranged from fatigue all the way to shortness of breath3.

Although, this can be seen as a small price to pay in treating cancer, further studies have gone to show that the approaches of chemotherapy and radiotherapy are able to “profoundly supress” the immune system thereby, causing the patient to become susceptible to other infections and disease4.

Outlining her recently published book, The First Cell, in a Wall Street Journal essay, she argues these approaches have been exhausted to their limit5. She claims that although 68% of currently diagnosed cancers are being cured, those with advanced stages of cancer have the same outcome compared to 50 years ago6.

While her solution to resolve the stagnation is to draw importance to detecting markers that early cancer cells release, such as proteins or genetic material, cancer vaccination remains a huge research interest. 

Prevention

Approximately 10% of the worldwide cases of cancer are caused by viral infection, with upwards of 80% of cases occurring within developing nations7. Viruses that are able to cause cancer, called oncogenic viruses, have the ability to disrupt DNA repair mechanisms or tumour suppressor genes which leads to an unstable genome and uncontrolled growth8.

HPV (Human Papillomavirus) infection is implicated in about 600,000 cases of cancer ranging from the regions of the cervix, anal, vulva, vaginal and penile cancers9.  The association factors between HPV and cervical cancers is higher than the association between smoking and lung cancer presenting a indisputable link between HPV infection and cancer incidence10. Therefore, in this case, vaccination against certain types of HPV provides protection from a wide range of cancers.

There are a range of HPV vaccines currently available for distribution since it was licenced in 200611. Specific vaccines such as Gardasil 9 (Figure 2)12 has been produced to protect against 9-known cancer causing types of HPV and shows excellent efficacy against cervical infection and the presence of cancerous tissues caused by these types of HPV13,14.

Figure 2: Gardasil 9 protects against nine known strains of HPV which is able to cause cancer following infection

A systematic review found that 95,000 participants showed decreased HPV related pre-cancerous cells 4 years after vaccination presenting its power to prevent the formation of more serious types of cancer15.

Despite this success, vaccination of other viruses that cause cancer, such as the Epstein Barr virus (EBV), have been difficult to develop.

Specifically, EBV goes through long periods of dormancy before it goes to cause cancer meaning that patients would need to observed for up to 30 years to evaluate the impact of vaccination16. Not only is this impractical, but it can also incur huge costs. Additionally, the virus preferentially infects humans, making animal models difficult to design which are generally used to test vaccines on.

Destruction

Cancer vaccination in existing patients with malignant tumours, however, is a much more difficult feat to achieve as cancer is highly different between individuals of the same disease type.

Much like regular vaccination, it harnesses the power of the patient’s own immune system. However, it differs in the way that it aims to relieve the suppression placed on the immune system by the cancer, so can identify and eliminate these cancer cells.

Provenge, one of the first personalised cancer vaccines, which is used within patients who have a specific type of prostate cancer underwent a rigorous 13-year clinical trial to become approved17. This vaccine is personalised as it extracts, modifies, and uses the patient’s own dendritic cells so immune cells can go and destroy cancer cells.

Dendritic cells love to show the rest of the immune system all the proteins from viruses or cancer cells that it has picked up allowing the real doers, T-cells, to mount an appropriate response18.

Using this, researchers identified that many prostate cancer cells express and release prostate acid phosphatase presenting a suitable target for the immune system19. When the dendritic cells are extracted from the patient (Figure 3)20, they are loaded with prostate acid phosphatase outside of the body and then re-introduced allowing T-cells to recognise and destroy these cancer cells that express the protein21.

Figure 3: Shows the personalised nature of the cancer vaccine Provenge against prostate cancer.

A systematic review presented that the Provenge treatment course led to a significant improvement in overall survival in prostate cancer patients compared to the control groups. Although, this treatment can give months more survival, it is incredibly expensive at £16,000 at a singular dose causing experts to raise questions about whether the current health care system can handle the personalised cost of cancer immunotherapy22,23.

Horizon

Cancer vaccination provides a powerful avenue of either prevention or destruction and has shown its effects both and inside and out of the clinic. Although, the success of the HPV vaccine presented how cancers caused by viruses can be altogether avoided, developing an EBV vaccine has revealed many practical challenges due to the nature of its life cycle.

On the other side of the coin, using vaccines to destroy existing malignant cells have been used within prostate cancer patients with positive results in relation to overall survival. Again, there is wide questioning of the costs as other cheaper, oral drugs came onto the market not soon after, with similar survival benefits24.

Both these practical and economic challenges aside, the recent approval of mRNA-based vaccines has opened another avenue for cancer vaccination25. If these approaches can be practical, cost-effective, and robust then it is another weapon in the arsenal we have against cancer.

References:

1.         Oncology, T. L. Valuing all lives equally: cancer surgery, COVID-19, and the NHS in crisis. Lancet Oncol. 22, 155 (2021).

2.         Immunotherapy. The John P. Hanson Foundation for Cancer Research http://www.hansoncancerfoundation.org/immunotherapy/.

3.         Pearce, A. et al. Incidence and severity of self-reported chemotherapy side effects in routine care: A prospective cohort study. PLoS ONE 12, (2017).

4.         van Meir, H. et al. Impact of (chemo)radiotherapy on immune cell composition and function in cervical cancer patients. Oncoimmunology 6, (2016).

5.         Raza, A. Cancer Is Still Beating Us—We Need a New Start. Wall Street Journal (2019).

6.         Democracy Now! “The First Cell”: Dr. Azra Raza on Why the “Slash-Poison-Burn Approach” to Cancer Has Failed. “The First Cell”: Dr. Azra Raza on Why the “Slash-Poison-Burn Approach” to Cancer Has Failed.

7.         Schiller, J. T. & Lowy, D. R. Virus infection and human cancer: an overview. Recent Results Cancer Res. Fortschritte Krebsforsch. Progres Dans Rech. Sur Cancer 193, 1–10 (2014).

8.         Luo, G. G. & Ou, J. J. Oncogenic viruses and cancer. Virol. Sin. 30, 83–84 (2015).

9.         Bansal, A., Singh, M. P. & Rai, B. Human papillomavirus-associated cancers: A growing global problem. Int. J. Appl. Basic Med. Res. 6, 84–89 (2016).

10.       Burd, E. M. Human Papillomavirus and Cervical Cancer. Clin. Microbiol. Rev. 16, 1–17 (2003).

11.       QA_HPV_General_EN.pdf.

12.       Ryan, B. Instagram Storytelling May Help Promote HPV Vaccination. Cancer Health https://www.cancerhealth.com/article/instagram-storytelling-may-help-promote-hpv-vaccination (2019).

13.       Cheng, L., Wang, Y. & Du, J. Human Papillomavirus Vaccines: An Updated Review. Vaccines 8, (2020).

14.       Moreira, E. D. et al. Safety profile of the 9-valent human papillomavirus vaccine: assessment in prior quadrivalent HPV vaccine recipients and in men 16 to 26 years of age. Hum. Vaccines Immunother. 14, 396–403 (2017).

15.       Jørgensen, L., Gøtzsche, P. C. & Jefferson, T. Benefits and harms of the human papillomavirus (HPV) vaccines: systematic review with meta-analyses of trial data from clinical study reports. Syst. Rev. 9, 43 (2020).

16.       Cohen, J. I., Mocarski, E. S., Raab-Traub, N., Corey, L. & Nabel, G. J. The need and challenges for development of an Epstein-Barr virus vaccine. Vaccine 31, B194–B196 (2013).

17.       Gardner, T. A., Elzey, B. D. & Hahn, N. M. Sipuleucel-T (Provenge) autologous vaccine approved for treatment of men with asymptomatic or minimally symptomatic castrate-resistant metastatic prostate cancer. Hum. Vaccines Immunother. 8, 534–539 (2012).

18.       Sallusto, F. & Lanzavecchia, A. The instructive role of dendritic cells on T-cell responses. Arthritis Res. 4, S127–S132 (2002).

19.       Rini, B. I. et al. Combination immunotherapy with prostatic acid phosphatase pulsed antigen-presenting cells (provenge) plus bevacizumab in patients with serologic progression of prostate cancer after definitive local therapy. Cancer 107, 67–74 (2006).

20.       Provenge is one of the best alternative treatment options for prostate cancer | SayPeople. http://saypeople.com/2012/04/15/provenge-is-the-best-alternative-treatment-option-for-prostate-cancer/ (2012).

21.       Anassi, E. & Ndefo, U. A. Sipuleucel-T (Provenge) Injection. Pharm. Ther. 36, 197–202 (2011).

22.       prostate-cancer-metastatic-hormone-relapsed-sipuleucelt-1st-line-id573-final-appraisal-determination-document2.pdf.

23.       SILVERMAN, E. Can we afford the war on cancer? Biotechnol. Healthc. 9, 13–16 (2012).

24.       Jarosławski, S. & Toumi, M. Sipuleucel-T (Provenge(®))-Autopsy of an Innovative Paradigm Change in Cancer Treatment: Why a Single-Product Biotech Company Failed to Capitalize on its Breakthrough Invention. BioDrugs Clin. Immunother. Biopharm. Gene Ther. 29, 301–307 (2015).

25.       mRNA Therapeutics & Vaccines: Immuno-Oncology – Moderna. https://www.modernatx.com/pipeline/therapeutic-areas/mrna-personalized-cancer-vaccines-and-immuno-oncology.

Image credits:

Syringe photo by Karolina Grabowska from Pexels

Lying on bed photo by Ivan Samkov from Pexels

Vaccine photo by cottonbro from Pexels

Test tube photo by Karolina Grabowska from Pexels

Horizon photo by Johannes Plenio from Pexels

Splitter icon by Freepik from www.flaticon.com

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