Modified 18 January 2024 by

How do cancer vaccines work?

Cancer vaccines are designed to help the immune system to recognise, attack and destroy cancer cells. Often, they’re personalised vaccines- meaning they’re specific to each patient and customised to the particular molecular mechanism causing the cancer.

The patient’s tumour sample is used to develop the vaccine. In people with cancer, the white blood cells known as T-cells do not work as normal. The cancer vaccine aims to act upon the irregular T-cells and regulate the antitumour response.

Cancer vaccine design: selecting cancer antigens

Any protein produced by a tumour due to its mutation can act as a tumour antigen. Tumour antigens are specific molecules or proteins found on the surface of cancer cells that can be used as biomarkers to identify the presence of a tumour. They are also crucial in developing vaccines designed to target and combat cancer. Tumour antigens are divided into two groups, including:

1) Tumour-associated antigens (TAA).

2) Tumour-specific antigens (TSA).

Tumour-associated antigen vs. Tumour-specific antigens

Tumour-specific antigens are found only in cancer cells. In contrast, tumour-associated antigens are found in high levels in tumour cells, but they might also be present at lower levels in healthy cells.

Cancer vaccines inside the body

Stimulating an immune response

The general way that a cancer vaccine works inside the body, once it’s been administered to the patient, is outlined below.

The vaccine is administered through an injection in the skin or muscle. Antigens or antigen creating genetic material in the vaccine, which are common to the patient's specific tumour, are released or produced in the body.

The immune system is triggered and activated to respond to the antigens, which are recognised as foreign. The immune response causes a cascade of immune cell reactions which attacks and destroys the tumour cells.

Once the tumour cells are destroyed, the immune cells eventually die but leave behind a memory of the antigens which are released upon the destruction of tumour cells. The memory of the specific cancer antigens prepares the immune system to recognise and attack potential future encounters of the same cancer antigens.

Novel mechanism of action for each type of vaccine

Virus vaccines

Scientists can change viruses in the laboratory so they cannot cause serious diseases. The altered virus is called a viral vector. Viral vectors can be recognised as foreign by the immune system, inducing potent immune responses. The immune system responds to the viral vector, helping the immune system recognise and respond to the cancer antigen.

Whole-cell vaccines

Cancer cells are used to produce cancer vaccines. They provide a source of tumour antigens; that's why they’re changed and grown in the lab to be later re-inserted into the patient.

Protein/peptide vaccines

These vaccines are made from unique proteins in cancer cells or small pieces of protein (peptides). They stimulate the immune system to attack cancer.

DNA/RNA vaccines

These vaccines are made by using specific segments of the genetic material, either DNA or RNA, typically present in cancer cells. These genetic segments are like unique signatures or identifiers characteristic of cancerous cells. They induce an immune response against tumour cells when injected into the body.

Dendritic cell vaccines

In the lab, scientists grow dendritic cells with cancer cells to make cancer-fighting vaccines. Dendritic cells capture invaders like bacteria, aiding the immune system to combat infections and diseases while training it to tackle cancer more effectively when the vaccine is used in patients.

Vaccine vector platform types

Vector vaccines utilise modified microorganisms such as viruses, bacteria, or fungi as delivery vehicles to stimulate an immune response in the body. These microorganisms are genetically engineered to carry a piece of genetic material from the target pathogen.

Other structures can also be used as vectors to deliver the tumour-associated antigens into the body.

Biomarkers to predict and optimise vaccine treatment

Cancer biomarkers are molecules in the body, and they can be detected either because the tumour releases them directly or because the immune system responds to the tumour by producing them. These biomarkers are crucial in diagnosing cancer, predicting its course, and monitoring treatment response. These biomarkers can be detected in serum (blood) samples.

Peptide vaccines against cancer can increase tumour-specific T cell responses, including a particular type of T-cell which kills cells infected with viruses- known as cytotoxic T-cells or killer T-cells. It has been reported that killer T-cell responses to multiple peptides after vaccination might be possible biomarkers for extended survival in vaccinated patients.

For example, some studies show that a high expression level of PD-1 on specific T-cells, known as CD4+ T-cells, may be a promising biomarker for predicting the prognosis of pancreatic cancer patients treated with a vaccine.

A person's lifestyle can cause changes in a person's gene activity, which impacts:

cell identity;
cell function;
vulnerability to diseases, including cancer;
response capacity of the immune system.

These profiles can be utilised as non-invasive markers for cancer risk, diagnosis, and prognosis as well as choosing and monitoring the effectiveness of cancer vaccines.

Some tiny molecules in the body, called microRNAs, can tell how the immune system is doing. By looking at these molecules, doctors can determine how well a vaccine or combination of treatments might work for you. It helps them plan the best way to treat your specific situation.

Tumour mutational burden (TMB)

The "tumour mutational burden (TMB)" refers to the number of mutations present in the DNA of a tumour cell. It is a measure used to assess the level of genetic mutations within a tumour. It can be important for understanding its characteristics and potential response to certain treatments, including immunotherapies.

TMB is one of the most commonly used biomarkers used to predict the patient outcome to immunotherapy. Cancer tumours with high levels of TMB are more likely to respond to treatment with immunotherapy. Patients with high TMB can be good candidates for neoantigen-based or peptide vaccine therapy.

In contrast, patients with low TMB can be treated better with vaccines based on tumour-associated antigens. Some tumours with low TMB express a low number of neoantigens and possess intense neoantigen-specific immunoreactivity, being an unsuitable target for neoantigen-based vaccines.

Combination therapy

Some studies show that cancer vaccines cannot elicit anticancer efficacy alone. Many have shown to be more effective in combination with other treatments that deactivate the mechanisms that suppress or weaken the activity of the immune system in the tumour environment.

Radiotherapy can enhance the recruitment of T cells into tumour tissue. In addition, other studies have shown that some chemotherapeutic drugs can enhance the anti-tumour activity of tumour vaccines.

Vaccines combined with immune checkpoint inhibitors or traditional treatments, can also induce more robust anti-tumour responses. Some studies show that vaccines in combination with a checkpoint inhibitor can provide the best setting to induce a potent anti-tumour immune response.

How does it work?