Types of cancer immunotherapy

The immune system is the body’s defence mechanism for clearing infections, pathogens and tumors. When our immune system is healthy and works well, it is able to seek out and destroy cancer cells. However, over a prolonged period of time (many years) tumors change (evolve) and develop mechanisms that allow them to escape immune control and grow – this is when a cancer becomes detectable on a scan for example.

Immunotherapy is a treatment that aims to boost the immune system and restore its ability to recognise cancer cells and eradicate them.

This type of therapy, which has renewed hope that one day cancer will be cured, works broadly via two main tactics:

The first one relies on isolating the patient’s own immune cells (particularly the so-called T cells which are the lynch pin for cancer immunity) from the blood, manipulating them in the lab to become more “killer-like” then infusing them back to the patient where they are now more efficient at destroying the cancer. One example of this approach is CAR(Chimeric Antigen Receptor)-T cell therapy which has been very effective in treating some blood cancers (e.g. diffuse large B-cell lymphoma, mantle cell lymphoma).

The second tactic works by administering drugs that weaken the barriers (checkpoints) that normally interfere with the ability of T cells to seek out and attack tumours, for example the drugs known as PD-1 and PD-L1 checkpoint inhibitors, which have shown efficacy in a wide range of cancers including melanoma, lung and head and neck cancers.

These treatments can work extremely well in some patients achieving disease control for many years and because of this, CAR-T cell and checkpoint inhibitor treatments have in recent years been approved for the treatment of various types of cancers.  

Other immunotherapeutic strategies are at various stages of development and include:

1. Vaccination with harmless tumour material in order to stimulate immune responses against the cancers with similar appearance – this is very much akin to a flu or polio jab.
2. Oncolytic viruses, which are viruses that infect cancer cells (but not normal healthy ones), destroy them and make them visible to the immune system (immunogenic).
3. Metabolic therapy, which aims to increase the “fitness” of T cells so they are able to fight cancer with more energy and vigour.
4. Cytokine treatment, which is akin to administering chemical signals (for example interleukin-2) that stimulate T cells, so they can be more active at attacking tumour cells.
5. Direct stimulators (or agonists) of T cells to further boost their ability to kill cancer cells.

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It is envisaged that some of these treatments will be used in a cocktail form (combination) to deliver a potent attack on cancer cells and simultaneously overcome several immunity hurdles at once in order to achieve the best outcome for immunotherapy.

Key to the success of immunotherapy is also the ability of the immune system to “see” the cancer, and because cancer cells are changing (or evolving) constantly they are often able to “hide” and escape immune attack. This is why strategies that aim to use immunotherapy alongside other more established treatments that cause cell death and expose the debris that results from that, making the cancer “visible”,  are also gaining much traction. For example, using combination treatment with radio- or chemotherapy to bolster the impact of immunotherapy.

Antibody-drug conjugates (ADCs) are also being tested as part of these cocktails. ADCs are molecules designed to seek out specific flags or “markers” found on cancer cells and at the same time have the unique feature of being loaded with a traditional cancer drug “warhead”. As such, these “conjugates” enable the selective killing of cancer cells decorated with these flags whilst sparing normal cells which don’t carry these markers. With this action, ADCs also stimulate a local immune response against the tumor potentially turning a cold tumor hot, which in turn increases the likelihood of success of an immunotherapy treatment if given at the same time (in combination).

It is clear that cancer immunotherapy is here to stay and a growing toolbox of tactics is being developed and deployed to boost the killing power of the immune system against tumors. Ongoing developments in this area will undoubtedly improve the way immunotherapy is used and maximise the benefits it can bring to patients.