Immune checkpoint inhibitors are a type of immunotherapy that has been recently used as a first-line treatment for lung cancer patients with metastatic disease. They are man-made antibodies that shut down key proteins on immune cells that, when turned on, can give cancer a free pass to spread.
For a sneaky disease like lung cancer that doesn’t show signs and symptoms till the late stages of the disease —which by then it has become stronger— immunotherapy can prove to be more effective than other conventional treatment options like chemotherapy or radiation therapy.
What are immune checkpoint inhibitors?Read More
Under normal conditions, the immune system possesses an elaborate skill in consistently surveilling the body and identifying foreign cells from normal cells. The reason for this is to keep the balance between protecting the body from foreign invaders and at the same time keeping it under balance to avoid attacking itself and causing an autoimmune disease.
The way this works is that the immune system cells recognize a mark called checkpoints that area on normal cells and missing on cancer cells. When an immune cell doesn’t find this mark, it deems this cell as a cancer cell or foreign cell and destroys it.
Scientists used this information and devised a way to use the immune system to target cancer cells through immune checkpoint inhibitors immunotherapy.
Dr. Scott Strome, Dean of the College of Medicine and Vice Chancellor for Health Affairs at the University of Tennessee Health Science Center says, “In order to know if you’re a viable candidate for checkpoint inhibitors as a treatment for your later-stage cancer, check with your doctor.”
Dr. Strome recommended that patients should first have their genetic code tested first by a healthcare professional before initiating treatment to determine the best treatment option available.
Types of immune checkpoint inhibitors to treat lung cancer
For non-small cell lung cancer, there have been a number of approved immune checkpoint inhibitor drugs, and these include the following:
PD-1 and PDL-1 binding switch off attacks from immune cells (t-cells). Sometimes, non-small cell lung cancer cells trick the immune system by raising the PDL-1 checkpoint on its surface, so when these t-cells find it, they bind to it and render it safe.
When the patient is infused with either PD1 or PDL-1 immune checkpoint inhibitors, they instantly find the PD1 receptor on t-cells or PDL-1 receptors on cancer cells and block their binding, which prevents the binding of both PD1 and PDL1 complex and stimulates the immune system to recognize and attack cancer cells.
Below is a table of the PD1/PDL-1 inhibitors that are FDA approved for lung cancer treatment:
Table 1. PD1/PDL-1 FDA approved drugs for lung cancer treatment
These drugs will be given through an intravenous injection every 2, 3, 4, 5, or 6 weeks and your doctor will decide whether this will be your only treatment or will be combined with other options like chemotherapy.
Another immune checkpoint inhibitor drug is Ipilimumab (Yervoy), but this one differs in its target. It works by blocking CTLA4 protein, which is found normally on t-cells, and keeps immune cells alert to fight off cancer cells and stop their growth.
Similar to PD1/PDL-1 inhibitor drugs, Impilimumab is also given intravenously once every six weeks. However, it should be combined with other treatments like chemotherapy or other PD1/PDL-1 inhibitors as it’s not used alone.
Immunotherapy can be a great option for many patients with advanced stage lung cancer. Immunotherapy is often better tolerated compared with traditional chemotherapy. However, immunotherapy can still have side effects and it is important to understand these side effects before starting immunotherapy.
Here’s a list of the most common side effects that can happen, organized from the most serious to the least serious:
Autoimmune reactions. These drugs can over-activate the immune system making it attack normal healthy cells like the liver, brain, kidney, and other important organs.
Reactions from the infusion. Since these drugs are given through an IV, some people may experience allergic reactions after the drug is infused, like itching, scratching, bleeding, or swelling.
Other less serious side effects. These include manageable side effects like diarrhea, nausea, coughing, fatigue, constipation, dizziness, joint pain, rash, and loss of appetite.
It is impossible to predict if patients will have side effects and what side effects they might have. But, if you’re being treated with any of these drugs, it’s important to share your symptoms and report any discomfort you might be experiencing, even if it’s mild, so that your doctor can figure out the best way to handle it.
Are they effective?
Given intravenously, these immunotherapy drugs essentially wake up the immune system and encourage it to recognize the protein and attack it. Because these drugs are aimed at a specific target, there are different and often fewer side effects than traditional chemotherapy.
When these drugs work, they work well. But they don’t work for everyone–at least not yet. Cancer researchers are now looking at ways to harness checkpoint inhibitors so that they work in even more people.
To know for sure if this particular type of immunotherapy will work for you based on your genetic code, ask your doctor. They’ll be able to tell you how you may react to the treatment.
Dr. Geoffrey Oxnard, thoracic oncologist, who focused his research efforts on lung cancer targeted therapies and novel diagnostics, shared with SurvivorNet that, “I have patients where the immune system has cleaned out the cancer. They’ve been on treatment for a couple of years. A couple more years go by, and they remain cancer-free from Stage 4 non-small cell lung cancer. That is the potential of immunotherapy.”
Oncology meets immunology — Another perspective
Dr. Oxnard also adds that most patients don’t get the response hoped for from immunotherapy, and the reason is not known to this day why some patients get great results while others don’t. He says, “We’re working very hard to figure out how to start with the backbone of immune therapy and make it better.”
Indeed, there have been continuous efforts to understand the discrepancies in outcomes for lung cancer patients after immune checkpoint inhibitor medications are taken. On paper, everything seems to work, but real-world evidence tells us otherwise.
So far, scientists have been experimenting with some techniques to improve immunotherapy efficacy for lung cancer patients. These include the following:
- Pairing up immunotherapy with chemotherapy or other conventional treatments
- Combining immunotherapies
- Using advanced molecular techniques to identify tumor structure
- Studying phases of the cell cycle
- Experimenting on regulators of cell cycle
- Conducting clinical trials
- Funding research efforts
Some researchers concluded that cancer cells will always find a way to trick the immune system. Because of this, it’s not enough to just produce a new drug or develop a new technology that targets cancer cells. But what’s more important is how to make cancer cells more sensitive to these drugs.
If cancer cells can be made vulnerable, they can be more easily managed and destroyed by immunotherapy or targeted therapy. The best way to achieve this is by pushing cancer cells into phases of the cell cycle prematurely.
It’s well-known that for cells to continue to grow and divide, they need to go through the several stages known as the cell cycle; the cell cycle is managed by regulators that push them from one phase to the next when they’re ready so that they can synthesize DNA to multiply. In the case of cancer cells, they multiply so fast and grow out of control because the cell cycle is affected and not functioning properly.
Thus, scientists are now working on a new angle to increase the efficiency of immunotherapy by weakening cancer cells as they grow and divide by recruiting proteins that are responsible for regulating the cell through phases of the cell cycle. This may also make cells more sensitive to other treatments such as chemotherapy, radiation therapy, and targeted therapies.
The Bottom Line
The exciting field of cancer immunotherapy continues to grow with new scientific discoveries that are made every day. Immune checkpoint inhibitors for lung cancer treatment have brought on a new paradigm in the field of oncology and showed great potential in enhancing the quality of life for lung cancer patients.
Despite great progress over the last decade more research is needed to continue to refine and improve these therapies so more patients can benefit.