Prof Carol-Ann Benn takes us into the wizarding world of immunotherapy spells and the wonder of these cancer-fighting drugs.
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Welcome to immunotherapy, the cancer equivalent of a defence against the dark arts class. I’m taking you back again into the wonderful wizarding world after our potions class a while back, and because we’re working out how your immune system plays a role in fighting cancer, I figured (with the help of my children who know a lot more about Hogwarts classes than me) what better analogy than a class about all the different defence tactics for fighting off the different varieties of evil and dark magic (cancer)?
Defence against the dark arts was literally a class teaching young wizards how to defend themselves against dark magic and this is rather like working out how your immune system plays a role in fighting cancer.
The immune system
Your immune system, although made up of both cell and humoral (fluid) components, is rather like the elements of a complex spell book and is more topical now due to COVID.
The immune system consists of many complex processes that involve your cells, organs and proteins that your body uses to fight cancers. Much like an army, the immune system detects and destroys abnormal cells trying to prevent and stop the growth of cancer cells.
Much like we saw with COVID (and people getting the virus despite vaccination), cancer cells look for ways to avoid destruction by developing genetic disguises, so they are less visible to the immune system (The Cloak of Invisibility). They may have proteins on their surface that turn off the immune system, a bit like a wand; or they may change the normal cells around the tumour (a cell spell), affecting how they respond to cancer cells.
Choosing your immunotherapy wand
This is why the concept of immunotherapy is so important. And understanding how to use your wand specifically chosen for you, is central to the success of casting the right spell to expel your cancer demon.
To aid this process, some pathology reporting systems already document immune activity comments such as finding immune cells around cancer cells. These cells, called tumour infiltrating lymphocytes (TILs), are a sign that the immune system is recognising the cancer. TILs on a path report are indicative of tumours that usually respond better to certain treatments.
So, different types of immunotherapy work in different ways and the field is forever-changing with scientists trying to work out how the different drugs affect the immune system and the cancer. And, to be honest this is why your chosen wand is particular to you and your immune system, and a critical part of why spell success works better with some people than with others.
The basis of spell art is in learning about how to defend, and how to attack against different opponents. Not only is it important to know what spells to use when, but proper technique is crucial to ensuring the spell works.
Immune checkpoint inhibitors are drugs that block immune checkpoints. Immune checkpoints are immune system roadblocks (blocking spells) that prevent your immune system from sending out too strong a response. This is like the Stunning Spell (Stupefy), not stunning as you’re so pretty, more zap – momentarily comatose.
The Protego spell
Cancers hide from the immune system by activating these checkpoints. Naturally these drugs block the roadblocks so that your immune cells can respond to the cancer. The Protego spell is the basic shield spell and is an effective roadblock.
Some of these roadblocks affect pathways (such as PD-1/PD-L1 and CTLA-4 pathways), and while there are many pathways (you should check with your oncologist), immunotherapy drug names you may have heard are pembrolizumab, atezolizumab and ipilimumab.
Many of these drugs are approved by the U.S. Food and Drug Administration (FDA) for specific cancers. Two of these are used to treat tumours that occur anywhere in the body if the tumour has a specific genetic change; this is called tumour agnostic treatment.
Pembrolizumab is approved to treat any tumours that have spread to distant parts of the body if they have a specific molecular change called microsatellite instability-high (MSI-H) or DNA mismatch repair deficiency (dMMR). Dostarlimab can also be used for this DNA mismatch.
The Expecto Patronum spell
This is a very powerful shield of positive memories to protect against dementors and other dark spells – need a happy, powerful memory to cast the spell and this is what your T cells are.
Your T cells are extremely clever magicians that fight most bad cells. T cell transfer therapy, also known as adoptive cell therapy, is like intense gym training for your immune cells as they are taken from your tumour, the ones that are the most active, and the best fighters are changed in a lab (by adding proteins, kind of like the gym bunnies’ special shakes) and grown in large batches and then can be sent back through your veins to fight the cancer.
A term for this treatment is chimeric antigen receptor (CAR) T-cell therapy used to treat certain blood cancers. A variety of side effects may occur with use, from fevers and low blood pressure to seizures (rarely).
The Expelliarmus spell
Part of your immune system army-fighting success is the ability to make antibodies when detecting something harmful. Antibodies fight infections by attaching to antigens (which are small molecules that start your body’s immune response). This would be like the Expelliarmus spell: disarm your opponent by making antibodies.
Antibodies are proteins. Monoclonal antibodies (therapeutic antibodies) are created in labs as immune system proteins; some of these attach to the cancer cells, creating a target for your immune system to kill the cell. They can block the activity of abnormal proteins in cancer cells and can also manipulate the tissue environment making it hostile for the cancer to grow. Monoclonal antibodies can also be grouped under targeted therapies because the drugs target cancer specific genes or proteins. The side effects are usually similar to allergic reactions.
Treatment cancer vaccines are created to boost your own immune system and work against cancer cells; these are different from vaccines that prevent cancer. Remember a vaccine is your immune system exercising in the field. This is done by exposing your immune system to recognise a foreign protein (antigen) and to recognise and destroy the antigen related to the substance. Vaccines can be used to prevent or treat cancer.
A cancer prevention vaccine is Gardasil which protects against human papillomavirus (HPV), a virus that can cause specific types of cancer, especially cervical (remember to get your youngsters vaccinated). It’s also useful for head and neck cancers.
A treatment vaccine example is a vaccine to treat advanced prostate cancer that doesn’t respond to hormone therapy.
Other useful treatment
Immune system modulators enhance your body’s immune system in either specific or general ways; they can be non-specific immunotherapies.
The confringo curse
This blasting curse requires cytokines that are immune system proteins that send messages between cells thereby activating the immune system. Two types of cytokines are used in cancer treatment.
Proteins called interferons are made by your immune system to alert your body that there is a pathogen (virus usually) in your body. These can be made in a lab to slow the growth of and fight cancer cells. Interferon alpha is one you may have heard about. These drugs when used may induce side effects such as flu-like symptoms, infections and rashes.
Another protein that can start an immune response by passing messages between cells is called interleukins; they have been used to treat melanoma and kidney cancer.
You may have heard bacillus calmette-guerin (BCG) in connection with tuberculosis. This immunotherapy is based on the BCG placed into the bladder through a catheter to activate the immune system to destroy tumour cells.
The SNaPe technique
Another cool technique is using viruses that have been changed in the lab to destroy cancer cells (the SNaPe technique…looks like a baddie but is a goodie). The virus enters the cancer cell, makes a copy of itself, causing the cancer cell to burst and die. The death of the cell releases proteins that activate your immune system so as to target any cancer cells that have the same protein as the killed cancer cell. By the way, the virus doesn’t enter healthy cells. Talimogene laherparepvec (T-VEC) is an example; this is a souped-up version of the herpes simplex virus, that little bugger that causes cold sores. It’s injected directly into little melanoma tumours.
Future trials will look at using different viruses, oncolytic ones (preferentially infects and kills cancer cells), these are the baddie-goodie ones, ensuring that more successful cancer treatments evolve.
The future of fancy spells
This was a little step into the world of immunotherapy. And, it really is a small step into the future of fancy spells where your immune system can aid in the fight against the big C that is trying to destroy your system by taking over your defence system first. So, to the big C, we are practising our defences against the dark arts until we graduate successfully.
MEET THE EXPERT – Prof Carol-Ann Benn
Prof Carol-Ann Benn heads up internationally accredited, multi-disciplinary breast cancer centres at Helen Joseph Hospital and Netcare Milpark Hospital. She lectures at Wits University and, in 2002, established The Breast Health Foundation.
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