An Introduction to Cancer Immunotherapy Treatments
Of all the things that your doctor could tell you that might be a cause for alarm, hearing that you have late-stage cancer is probably one of the worst. We’ve all heard people talk about a “cure for cancer” when in fact there is no one single cure. However things are starting to look up now. According to the National Cancer Association, between 2011 and 2015, more new treatments were approved for lung cancer (the second most common type of cancer) than during the four-decade period prior to that.
Eventually we will get to the point where any stage of cancer is manageable through the administration of various drugs and therapies in much the same way that diabetes is manageable. Until we get to that point however, the closest thing to a cure for cancer might be something called “cancer immunotherapy”. According to Professor Roy Herbst, chief of medical oncology at Yale Cancer Center, “immunotherapy could replace chemotherapy as the ‘standard treatment’ for cancer within the next five years“. One research group reckons that there are over 2,000 products currently in active development in the cancer immunotherapy pipeline – nearly 40% of the entire oncology pipeline.
Defining Cancer Immunotherapy
As investors, we need to have a basic understanding of what immunotherapy entails without boring ourselves to tears. First, let’s review what cancer is:
- Some of the body’s cells begin to divide without stopping and spread into surrounding tissues
- Since they are body cells, the immune system has a hard time recognizing them at first
- Once recognized, the immune system may be too weak to fight the cancer cells
- Cancer cells are extremely clever and have all kinds of ways to trick your immune system
Now let’s move on to immunotherapy. The simplest definition for immunotherapy is as follows:
Immunotherapy is treatment that uses certain parts of a person’s immune system to fight diseases such as cancer
While that is easy enough to understand, the terminology starts getting thick in a hurry. It turns out that the term “immunotherapy” can mean many things to many people depending on the type of immunotherapy being discussed. Let’s look at five types of cancer immunotherapy treatments.
Monoclonal Antibodies (mAbs)
An antibody is a protein that the immune system uses to identify and neutralize foreign objects like bacteria and viruses. Researchers can design antibodies that specifically target certain cancer cells. They can then make many copies of that antibody in the lab which is what the word “monoclonal” is used in reference towards. The antibodies are then injected into the patient so that their immune system can recognize cancer cells that it wasn’t able to previously. Monoclonal antibodies (mAbs) can also be used for other diseases in addition to cancer. The first mAbs drug was approved by the FDA in 1986 and since then more than 75 drugs have been approved (click here for a complete list).
Your immune system has to spot invading molecules like bacteria and viruses while at the same time knowing which of your own cells not to attack. To keep itself under control, your immune system has molecular brakes called “checkpoints”. Cancer cells sometimes take advantage of you by turning these checkpoints off so they can hide. Immune checkpoint inhibitors are drugs designed to release these “brakes” and let your immune system kick the isht out of those cheeky cancer cells. The first drug of this sort was approved in 2011 (ipilimumab), and since then at least 5 more drugs have been approved:
Just to show how effective these types of treatments can be, we came across an interesting story about a gentleman who all but cured himself of cancer working closely with the great people over at Cancer Commons while taking Opdivo along with radiation. If that doesn’t impress you, check out this story of someone taking a combination of epicadostat (in trials now) and Keytruda:
The 67-year-old man had been a heavy smoker for 50 years and was diagnosed with advanced lung cancer. He had already undergone aggressive rounds of chemotherapy and radiation, but the results were only temporary. His cancer had metastasized to stage 4 and was spreading throughout his body.
“He was very thin, barely able to walk, and was having trouble breathing. I was afraid that his lifespan would be severely reduced, as his large tumor consumed a large portion of his lung, which impaired his ability to walk and made surgery to remove it impossible,” Wasser said.
Now, a little over a year after starting his treatment in the ECHO-202 trial, the tumor has regressed significantly and doctors can barely find it.
How amazing is that?
We’re probably all familiar with how vaccinations work. You get an injection of a substance that your immune system recognizes as something bad so that if you ever encounter the actual bad thing in the future, your immune system is prepared. That’s called a preventative vaccination. Unfortunately, there are only a few cancers that you can prepare in advance for, like cervical cancer, which is one of very few cancers that is caused by a virus. Approved in 2006, Gardasil is a vaccine that prevents cervical cancer but can’t be used for anyone who already has cervical cancer. Vaccines used for treating cancers that already exist are called treatment vaccines.
Two types of cancer preventive vaccines (human papillomavirus vaccines and hepatitis B virus vaccines) are available in the United States, and one treatment vaccine (for metastatic prostate cancer) is available. (Source: National Cancer Institute)
Treatment vaccines are substances that are introduced into your body that stimulate your immune system to attack tumor cells. They can be made of dead cancer cells, proteins or pieces or proteins from cancer cells, or immune system cells. Researchers are working on several right now, but only one is approved. Sipuleucel-T is a $100,000 vaccine used to treat advanced prostate cancer that doesn’t respond to other therapies. However, the real value add here might be in the form of personalized vaccines made possible by using artificial intelligence. Cathy Gutierrez over at Harvard University published an excellent blog post on the topic which included the below diagram which explains everything in terms so simple that even an MBA could understand them:
According to that blog post, the process you see above takes about 6 weeks and costs about $60,000. While that price point may be out of range for most patients, it still points towards a clever way to treat cancer that will become quicker and cheaper as technology continues to improve.
Adoptive Cell Transfer (ACT)
Adoptive Cell Transfer (ACT) is the transfer of cells into a patient. These can be the patient’s own cells – collected from their blood or directly from their tumors – or even another person’s cells. There are three primary approaches to ACT that are being tested in human clinical trials:
- Chimeric Antigen Receptor (CAR)
- T Cell Receptor Ligation (TCR)
- Tumor Infiltrating Lymphocytes (TIL)
You may have seen the term “CAR-T” used before when discussing certain biotech stocks and that’s because it’s the approach that is the furthest along. In this treatment, the doctor takes the patient’s T cells – a type of white blood cell – and then modifies the genes in the T cells to make them more effective in attacking the cancer cells. Then, large batches of these genetically modified cells are grown in the lab. Finally, the supercharged T cells go back into your body through an IV infusion. The approach has proven to shrink some tumors in a broad range of cancers, including melanoma, leukemia, and prostate cancer.
The first FDA approval for a CAR-T drug was in August 2017 when tisagenlecleucel was approved for use against acute lymphoblastic leukemia with a price tag of around $475,000. Since then, one more CAR-T drug was approved and a number of others are in various stages of approval as seen below:
It’s interesting to see how gene editing and artificial intelligence are being used to accelerate the effectiveness of various cancer immunotherapy treatments like CAR-T and cancer vaccines. Expect that to accelerate even more as the price of gene sequencing falls and artificial intelligence algorithms constantly improve over time.
Hang in there because we’re almost done now. Our last category is something called “cytokines” and they’re a group of proteins in the body that help boost the immune system. It’s at this point that things get incredibly complicated and confusing, so we’ll keep it simple and just give you some keywords that you can use during your next cocktail party. Interferon and interleukin are two types of cytokines found in the body that have man-made versions now that are injected into your body in much the same way you’d mainline some good quality smack. If all goes well, here’s what we can expect these immunotherapy drugs to do (props to Cancer Research UK for providing the below):
- Interfere with the way cancer cells grow and multiply
- Stimulate the immune system and encourage killer T cells and other cells to attack cancer cells
- Encourage cancer cells to produce chemicals that attract immune system cells to them
You might be reading this article because you or someone you love has one of the +200 different types of cancer that exist today. You may feel helpless and discouraged to find out that cancer immunotherapy is an expensive venture. These drugs can run upwards of $10,000 a month. If price becomes an issue, you may consider finding a clinical trial that you can participate in. We put together a handy article on how to find the latest and greatest clinical trials near where you reside.
If you’re reading this article because you’re an investor, take a look at our article published a while back on immunotherapy stocks. We can’t say we’re overly thrilled with how the “Loncar Cancer Immunotherapy Index” has performed:
Be aware that biotech stocks are risky ventures. Of course for all the people out there “investing” in cryptocurrencies, these stocks are about as risky as T-Bills (look it up). Also, consider that the real opportunities may not even be publicly traded. According to the bright minds over at CB Insights, immunotherapy deals now account for 62% of all investments in cancer therapeutics startup companies. Stay tuned for a coming article where we deep dive into some of the more exciting immunotherapy startups out there.
In loving memory of Steen Andersen…