A pharmaceutical company recently unveiled their plan to commence phase 3 clinical trials next month, for their industry-leading personalised cancer vaccine for patients with melanoma [1]. It is the first vaccine of its kind to reach this milestone and demonstrates the utility of vaccination approaches beyond infectious diseases. This article aims to provide a brief introduction to cancer and give some insight into the current state of cancer vaccine technology.

Cancer is a collective term for diseases that are caused by cells dividing uncontrollably and gaining the ability to spread to other parts of the body. Healthy cells can become cancerous by acquiring mutations in their genome, or as a result of certain viral infections that hijack the cellular machinery. As cancer cells multiply, they can form a mass known as a tumour and interfere with the proper functioning of the affected organs – this is what makes cancer a leading cause of death worldwide [2]. Approximately 40% of the general population is predicted to develop cancer at some point in their lifetime [3]. Nevertheless, that percentage would be even higher if it were not for our immune system, which is able to recognise and clear mutated cells from the body before they can become malignant.

One of the primary functions of the immune system is to distinguish unhealthy cells (such as virus-infected cells, or cancer cells) from healthy cells, and eliminate them. Immune cells check that a cell is healthy by inspecting the proteins on the cell surface to make sure they are normal [3]. The mutations in cancer cells cause them to make abnormal proteins that should act as antigens and trigger an immune response, but sometimes they can go undetected [4]. This can happen when the mutated proteins are not sufficiently different from normal proteins so the immune cells do not recognise them as abnormal. It can also be the case that the mutated proteins are not present in a large enough amount for the immune cells to notice them [4, 5]. In addition, cancer cells are able to keep immune cells away to varying degrees, by sending out inhibitory or restraining signals that prevent them from mounting a successful immune response. This is where cancer vaccines can help. When combined with drugs that reduce the inhibitory signals, cancer vaccines can help the body raise a strong immune response against those mutated proteins that it previously could not recognise.

Nowadays, young people in many countries receive the Human Papillomavirus (HPV) and Hepatitis B virus vaccines. These viruses can cause cancer, so by vaccinating against them, it is possible to prevent certain types of cancer. However, most cancers are not caused by viruses but by the random accumulation of mutations in our cells [6]. Every cancer gains a unique combination of mutated proteins, which means that even if two cancers from the same tissue were to be compared, such as any two lung tumours or any two breast tumours, they would still have an entirely different genetic makeup. This makes cancer vaccines more complicated to develop than vaccines against one specific infectious agent such as a virus [4, 7]. Since it is impossible to predict which antigens any individual’s cancer will express, most cancer vaccines are delivered therapeutically – meaning they are administered after the cancer has already formed. Unlike conventional preventative vaccines (like the flu jab or the prenatal DTaP vaccine – see our previous article), which are designed to prevent the patient from developing a disease, therapeutic cancer vaccines cannot prevent the cancer from forming. Instead, the goal is to help the immune system recognise and cure the existing disease.

Despite these challenges, several cancer vaccines are already on the market, and more are being developed. Up until recently, patients with cancers of the same origin (e.g. all bladder cancer patients) would receive the same vaccine [8, 9, 10]. However, due to the genetic diversity of cancer, “one-size-fits-all” treatments like these do not work optimally in every patient. Now, testing is well underway for a variety of personalised cancer vaccines, some of which share the same mRNA technology as the Pfizer or Moderna COVID-19 vaccines (check our previous article on mRNA vaccines) [11]. Because mRNA vaccines are easier to produce than traditional ones, it is possible to encode multiple cancer antigens in a single vaccine, making the treatment more potent and potentially reducing the required frequency of dosing [11, 12]. Each vaccine is generated based on the genetic sequence of the individual patient’s cancer. A computer programme is used to select the mutated proteins that are most likely to elicit a strong immune response [11]. By selecting only those proteins that are mutated, it is possible to reduce the risk of side effects affecting healthy tissues. There are many different types of personalised cancer vaccines in clinical trials, but those based on mRNA are currently the furthest ahead in their development.

When combined with a cancer drug against melanoma, the aforementioned personalised mRNA cancer vaccine led to a 44% reduced risk of recurrence or death as compared to the existing drug used on its own, as stated by its producers [11]. While melanoma is known to respond well to treatments that activate the immune system, it is hoped that these vaccines will also be effective in other types of cancer [13, 14]. Clinical trials are already underway to test whether personalised cancer vaccines can work in a variety of other solid tumours, including lung and colon cancer [15, 16].

Although these approaches are still in the early stages of development and have their own limitations, they nevertheless represent an exciting development in the field of personalised medicine.