What is Immunotherapy ?

Ever since I was diagnosed as Stage 4 - and saw the published 10% survival stats - I´ve been saying that my strategy is to try and stay alive long enough for some of the new treatments to come of age. My recent recurrence came as a bit of a shock. I was hoping to be cancer free for a few years after 1st line treatment, so when another tumour was found only 10 months after I finished 1st line treatment it totally destroyed my confidence in my strategy.

Right now, the biggest hope for new cancer treatments is immunotherapy. I had not invested much time in understanding immunotherapy because, like I said above, I thought it would be a while before I´d even have to consider it. However the recurrence has meant that immunotherapy might be on the cards for me much sooner than I anticipated. I´ve been trying to school up, but I´m also struggling to explain immunotherapy to family and friends.

So, here´s my attempt at a 101 explanation of immunotherapy and specifically what it might mean for me. If you´re an immunotherapy guru and you think I´ve got something wrong or missed something, please do let me know.

What is Immunotherapy ?

Immunotherapy isn´t one specific treatment, it´s better described as a class of treatment that helps your own immune system fight cancer i.e. rather than killing it which externally introduced ´agents' like radiation and chemotherapy.

Cancer, unlike the vast majority of other illnesses that affect us, is able to hide from your immune system. Some immunotherapies work by marking cancer cells to alert the immune system and spark it into action. Other immunotherapies just boost your immune system to work more effectively against cancer.

Types of Immunotherapy ?

Lets use the distinction I mentioned above to segment the different types of immunotherapy i.e. (1) those that help the immune system directly attack the cancer, and (2) those that generally boost the immune system.

Types of immunotherapy that help the immune system act directly against the cancer include:

  • Checkpoint inhibitors. These are drugs that help the immune system respond more strongly to a tumour. These drugs work by releasing “brakes” that keep T cells (a type of white blood cell and part of the immune system) from killing cancer cells. These drugs do not target the tumour directly. Instead, they interfere with the ability of cancer cells to avoid immune system attack.

    • What does it mean for me: Checkpoint inhibitors can be used only in colon cancer patients who have tested positive for certain gene changes. The most common test is for a high level of microsatellite instability (MSI-H), or changes in one of the mismatch repair (MMR) genes. Like 85% of colon cancer patients my MMR is normal so its unlikely that drugs like Pembrolizumab (Keytruda)  and nivolumab (Opdivo) will work for me. These are drugs that target PD-1, an immune system protein. I am however waiting on a more comprehensive gene panel. There is a very small chance (~3%) that I might turn out to have a high tumour mutation burden (TMB), in which case these drugs might work for me.

  • Adoptive cell transfer: This is a treatment that attempts to boost the natural ability of your T cells to fight cancer. T cells are taken from your tumor. Then those that are most active against your cancer are grown in large batches in the lab. The process of growing your T cells in the lab can take 2 to 8 weeks. During this time, you may have treatments such as chemotherapy and radiation therapy to reduce your immune cells. After these treatments, the T cells that were grown in the lab will be given back to you via a needle in your vein. CART T has one adaptive cell transfer technique that has got a lot of media attention because of its dramatic results in otherwise hopeless situations. Incidentally, the Peter MacCallum Centre in Australia is leading the way on CART T globally.

    • What does it mean for me?: CAR T is very exciting, and lots of friends have emailed me about it. Unfortunately right now it can´t be used for solid tumours. All the big successes have been for Leukemia and Lymphomas. There are however clinical trials looking at this.

  • Monoclonal antibodies. There are immune system proteins produced in the lab. These antibodies are designed to attach to specific targets found on cancer cells. Some monoclonal antibodies mark cancer cells so that they will be better seen and destroyed by the immune system, and these are a type of immunotherapy. Other monoclonal antibodies that are used in cancer treatment do not cause a response from the immune system. Such monoclonal antibodies are considered to be targeted therapy, rather than immunotherapy.

    • What does it mean for me?: There are several monoclonal antibody treatments already approved for use in Colon Cancer. Honestly - I´m unclear whether these are technically immunotherapy or just targeted therapy, Í´m pretty sure they are the latter.

      • Bevacizumab (Avastin): a monoclonal antibody that targets the VEGF/VEGFR pathway and inhibits tumor blood vessel growth; approved for subsets of patients with advanced colorectal cancer, including as a first-line therapy. I´m eligble for this and I suspect at some point it will be a part of my treatment regime. However right now, because I don´t have an active tumour, it has not been recommended.

      • Cetuximab (Erbitux) & Panitumumab (Vectibix): monoclonal antibodies that target the EGFR pathway; approved for subsets of patients with advanced, EGFR-positive colorectal cancer, including as a first-line therapy. I am eligible for this but it would probably used later on for me.

  • Treatment vaccines, which work against cancer by boosting your immune system’s response to cancer cells. Treatment vaccines are different from the ones that help prevent disease.

    • What does it mean for me?: I´m not aware of any vaccines for Colon Cancer however I do know of at least one clinical trial looking at different vaccine agents.

Types of immunotherapy that enhance the body’s immune response to fight the cancer include:

  • Cytokines. These are proteins made by your body’s cells. They play important roles in the body’s normal immune responses and also in the immune system’s ability to respond to cancer. The two main types of cytokines used to treat cancer are called interferons and interleukins.

    • What does it mean for me?: Not aware of any relevant treatment options here.

  • BCG, which stands for Bacillus Calmette-Guérin, is an immunotherapy that is used to treat bladder cancer. It is a weakened form of the bacteria that causes tuberculosis. When inserted directly into the bladder with a catheter, BCG causes an immune response against cancer cells. It is also being studied in other types of cancer.

    • What does it mean for me?: Not aware of any relevant treatment options here.

Clinical Trials

As you can see above there is no transformative treatment option for me in the immunotheraphy family right now. There are however literally hundreds of clinical trials underway, many of which are focussed on immunotherapies.

One of the things I don´t understand yet is how clinical trials work. How do Australian institutions decide what to trial ? Can I participate in US or European trials if I´m willing to fly there ?

Comprehensive Gene Panel

I´ve paid several thousand dollars (not covered by Medicare or private health insurance) to have a comprehensive gene panel done on the tumour that was recently removed. The Peter MacCallum Centre in Melbourne is - to my knowledge - the only place in Australia that can do these panels. I know the report will be very informative, but the odds of it leading to specific treatment decisions is very slim. I still think it´s worth the money, because as more clinical trials crop up, having a better understanding of the genetic profile of my cancer is going to be really valuable.

So…still lots to figure out, but as I said earlier, I feel like I need to get this figured out sooner than I had been anticipating.