What is immunotherapy?

Using the body’s own defences against cancer.

Immunotherapy is a way of boosting or using our body’s own immune systems ability to fight cancer. There are several different types of immunotherapy being developed. Some are still in the very early stages but are very exciting ideas and you will often see stories in the media about them as the latest treatment. Others are now being used to treat patients.

What is immunotherapy

The simplest is to generally boost the activity of your immune system. Cytokines are chemicals that regulate your immune response. Cytokines such as interferon alpha (IFNa) and Interlekin-2 (called aldesleukin) stimulate your immune system to attack cancer cells. IFNa isn’t used much now as it causes unpleasant side effects, but aldesleukin is currently used for kidney cancer and is being tested for use in other cancers.

Your immune system is constantly checking for and destroying anything that could cause you harm. This includes bacteria, bacterial toxins, viruses, and also cancer cells. 

On the surface of every cell are molecules made of protein, called antigens that are used to help recognise if they are our own cells or an invader. A bit like a flag. If your immune system sees an unknown antigen it will be primed to destroy any cell with that antigen. When cells become cancerous they often make new, unique antigens, so your immune system will recognise them and destroy cancer cells they are attached to. Unfortunately this doesn’t always work.

One of the most recent to appear in the news are vaccines (mRNA vaccines hit the headlines when they were used against COVID-19). Vaccines usually work by showing your immune system antigens from a disease so that it becomes quicker and better at getting rid of infections before they make you ill. Cancer vaccines help your immune system be better at recognising and destroying a cancer you already have. 

These vaccines can be made from the antigens themselves made in a lab, or complete cancer cells from a patient. Sometimes your body is given the information for making the antigens itself to activate your immune system. This is done either by using something called mRNA or borrowing a handy feature of viruses.

The instructions for everything a cell makes are held in its nucleus, written in the molecule of DNA. These instructions never leave the nucleus, but the machinery to make proteins like antigens is outside the nucleus. To get round this problem the cell copies the instructions for the bit it needs as a substance called mRNA (m is short for messenger) which is sent out of the nucleus to where it is used. mRNA vaccines inject these instructions into your body where for a short time it will make the antigens to activate your immune system. As yet, mRNA vaccines are still in clinical trials and are not routinely used.

Viruses work by infecting our cells and taking over the manufacturing machinery forcing them to make all the parts for new viruses. Some cancer vaccines are being made by adding the cancer antigens to the viruses that have been made harmless, but they still take over cells and make them make the antigens for the immune system to recognise.

An important part of your immune system are proteins called antibodies. These are made by a type of white blood cell, the B-cells. Antibodies recognise and bind to antigens on bacteria or cancer cells and label them for destruction by the immune system. They can also be made to bind to many different molecules which makes them very useful tools in treating cancer. 

In a lab, scientists can produce large amounts of a single type of antibody (mono means single – clonal means copies). Monoclonal antibodies, or MABs can be given directly to a patient through a vein where they bind to cancer cells and trigger an attack by the immune system. (e.g. Herceptin and Mabthera). By adding a cell killing drug or a radioisotope they can be used to deliver treatment directly to cancer cells. They can also be used to block messages from chemicals that make cancer cells divide or grow blood vessels to supply them with oxygen and nutrients (e.g. Avastin).

Your immune system has a system that prevents you from attacking your own cells. Some cancer cells take advantage of it by releasing chemicals that stimulate this effect, so the immune system ignores them. Researchers have made drugs called checkpoint inhibitors that block this action. Specific MABs block these chemicals, allowing your white blood cells to be activated and attack the cancer cells. Examples of this are Keytruda and Avelumab.

Your immune system includes a second type of white blood cell, called a T-cell which can attack and destroy infections and cancerous cells. In order to do that it needs to be able to recognise antigens on the surface of cancer cells. T cells have antibody-like proteins on their surface that bind to antigens, triggering their cell killing activities. These are called receptors. 

Our T-cells have the receptors to recognise many different antigens, but they can’t always recognise cancer antigens. CAR-T therapy takes T-cells out of your body and changes them to add the right receptor as well as a switch to make sure the T-cell is properly activated when it recognises a cancer antigen. 

There are several hundred CAR-T trials happening at the moment, and there are a few approved therapies, mostly for lymphomas (e.g. Kymria) and myelomas (e.g. Abecma) as it can be difficult for the CAR-T cells to get into solid tumours.

In order for these advances to be made available to people with rare cancers, researchers need to be able to study their specific tumours, in order to find antigens that can be used to build new immunotherapies and then test them in a clinical trial. This is challenging when there are few patients with a particular cancer. RareCan aims to speed up the process by collecting the relevant information about patients who are interested in taking part in research.