Can we Vaccinate Cancer? — Lay article

It has long been thought that to vaccinate, we protect ourselves before we are at risk of becoming ill. Scientists study the illness-inducing bacteria or virus (pathogen) and identify unique structures on the surface of the pathogen. Our immune system is then able to target and kill these pathogens due to the increased production of antibodies following vaccination before a patient can become sick. Now imagine if the reverse was true. Imagine a patient develops a condition such as cancer, which scientist then study for unique structures only found on the cancerous cells and not on healthy cells. So, could scientist develop a vaccine which targets these cancer-specific structures and kill cancer cells?

A team of German doctors lead by Dr Dörrie from University Hospital Erlangen evaluated and reviewed the risks and benefits of a new cancer vaccine. The results or the review, published in January 2020, were based on multiple studies which include 781 patients with different types of cancer. The aim for the team was to answer the titled question which has been puzzling scientists since the turn of the century.

This latest vaccine should allow patients to use their immune system to understand and recognise every aspect of a cancer cell’s mutated DNA. This could be achieved by taking a sample of cancerous genetic information, in the form of mRNA, taken from a biopsy. The mRNA is then inserted into a patient’s dendritic cell (DC) — initiators of the adaptive immune system which produces antibodies. The mRNA-loaded DC is then grown in a test tube before it is injected back into the patient. In theory, this method should then activate the adaptive immune system to produce antibodies which can target and kill cancer cells.

There has been vigorous discussion regarding the development of a vaccine which can target and kill specific cancer cells among cancer doctors for the past two decades. Dr Geert-Jan Boons discussed therapeutic cancer vaccines during a Tedx talk seminar at the University of Georgia, USA. Dr Geert-Jan Boons perfectly summarised the importance of why a cancer vaccine should be available to patients back in March 2013. Dr Boons said on the topic, “If we could train our immune system to make antibodies… that very specifically binds to the cancer cell surface, we may with very high selectivity target those cancer cells, kill them and cure the patient.” Seven years later, and researchers may finally be on the cusp of developing a vaccine which can specifically target and kill cancer cells.

The idea of vaccinating against cancer cells has been a topic of discussion amongst cancer specialist since the 19th century when William Coley conducted the first study back in 1891. The American surgeon attempted to inject bacteria into solid tumours to kill cancer cells. Coley’s study brought about a 10% clinical response rate, revolutionary at the time. Unfortunately, further studies could not improve the clinical response rate, leading to radiotherapy and chemotherapy becoming the preferred method to manage cancer patients throughout the 20th century.

In the present study, Dr Dörrie and her team had the aim to review the safety profile and clinical effect of mRNA-loaded DC in cancer patients. The unique aspect of the review lead by Dr Dörrie was that mRNA was loaded into DC via electroporation — the process of using electrical pulses to create temporary holes in the cell surface of DC, allowing cancerous mRNA to pass into the cell. Previous studies which have tried to research the clinical effect of mRNA-loaded DC for cancer patients used other methods to insert cancerous mRNA into DC. However, these methods were only able to allow an insufficient amount of mRNA to pass into DC, creating an ineffective cancer vaccine.

The safety profile of mRNA-loaded DC shows that the vaccine is generally safe and well-tolerated amongst 99% of patients who used the drug. There most common side-effects were flu-like symptoms (fever, headache, chills, muscle pains) and tiredness. These side-effects are common following vaccines and are signs that the immune system has been activated. In most patients, these side-effects were mild and passed without medical attention. Mild vitiligo was the only autoimmune disorder which presented in just one patient during clinical trials. Although cosmetically disturbing to some patients, a harmless condition which has no impact on a patient’s day to day life. Other autoimmune disorders such as thyroiditis have been associated with DC vaccines. However, as the vaccine in the trial was not produced using the same method as mRNA-loaded DC vaccines, we cannot assume there is a link between mRNA-loaded vaccines and autoimmune disorders.

mRNA-loaded DC vaccines were shown to be almost 2x more clinically effective than other types of cancer vaccines. Across the 12 types of cancer in which mRNA-loaded DC vaccines were studied, melanoma and non-Hodgkin’s lymphoma showed the most significant clinical effect. When looking to assess the clinical benefit of a drug, researchers considered how many patients had their cancer completely removed, partially removed, or no longer growing. Assessing the benefit of mRNA-loaded DC vaccines using this definition, melanoma patients experienced a 30% clinical benefit from the vaccine. It should also be mentioned that patients with early-stage cancers had a greater clinical impact following mRNA-loaded DC treatment compared to patients with late-stage cancers.

We haven’t found the cure to cancer just yet. But the results of this study show why it may become beneficial to vaccinate some patients against their cancer before the end of the decade. Many scientists are already speculating the possibility of combining mRNA-loaded DC with chemotherapy or other types of anti-cancer vaccines to further improve survival rates of cancer patients. Judging by the results of this study anyway, immune and cancer specialist are right to be excited by the advancements in the search for a vaccine to cure cancer.

DISCLAIMER — the content of this blog is the synthesis of publicly available new stories, and is not intended as promotion of any prescription-only medication within the UK or elsewhere in the world.

Reference:

Dörrie, Jan, et al. “Therapeutic Cancer Vaccination with Ex Vivo RNA-Transfected Dendritic Cells — An Update.” Pharmaceutics, vol. 12, no. 2, 2020, p. 92., doi:10.3390/pharmaceutics12020092.