Checkpoint inhibitors as a form of treatment for cancer have gained a lot of traction in the last 10 years. A subset of immunotherapy, Checkpoint Inhibitors prevent a person’s immune system from turning off if cancer cells are identified in the body. In simple words, they block the checkpoint proteins and give permission to the healthy cells of the body to continue fighting cancer. One of the key functions of the immune system is to differentiate between the healthy cells of the body and any foreign agent that may bring us harm and problems. This process then makes sure that the immune responses of the body can get rid of any foreign substances while sparing the healthy cells of the body. 

In order to differentiate between the two types of cells, the immune system uses checkpoint proteins that are present on the surface of the cells. One can think of these checkpoints as something similar to a switch that needs to be turned ‘on’ or ‘off’ to trigger an immune response. However, things get a bit complicated when it comes to cancer cells. Due to the fact that cancer cells are the body’s own cells that have mutated, the immune system doesn’t always recognize them as a foreign entity. The cancer cells in a patient’s body use these very same checkpoints to avoid being attacked by the immune cells. 

Along with this, these cancer cells also send deceptive signals at the checkpoints that tell the T-cells of the body that they are not harmful. This is where checkpoint inhibitors come into play as these drugs are curated in a way that enables them to target checkpoint proteins. Since checkpoint inhibitors are a subset of immunotherapy, they don’t directly kill the cancer cells but instead boost the immune system to find and locate these cancer cells, in order to ensure the immune responses can attack them comprehensively. 

Types of Checkpoint Inhibitors

In order to assign a specific checkpoint inhibitor to a patient, experts will look for biomarkers or some genetic features that will highlight how a drug will bring a positive outcome for that patient’s specific needs. These biomarkers include a PD – L1 protein and CTLA-4 protein. PD-L1 is a protein that is often found in cancer cells. When the PD-L1 protein on a cancer cell binds with the PD-1 protein on the immune cell, the cancer cell is left alone and deemed to be healthy. Drugs that target PD-1 protein include Pembrolizumab (Keytruda) and Nivolumab (Opdivo). To fulfill the criteria for the prescription of these drugs, a patient should exhibit large amounts of the PD-L1 protein on the cancer cells in the body. These drugs then expose the cancer cells leaving them to be attacked by the healthy cells. 

LAG-3 inhibitors are another type of checkpoint inhibitor that is used to treat cancer. LAG-3 is the type of checkpoint protein that is found on some immune cells and they help to keep the immune responses of the body in check. Relatlimab is a drug that binds itself with the LAG-3 protein and helps to boost the body’s immune responses thereby helping to fight cancer. 

What Kind Of Cancers Are Treated With Checkpoint Inhibitors

Many cancer treatments include checkpoint inhibitors. These include, but are not limited to: 

1. Bladder Cancer – Checkpoint Inhibitors are generally given for advanced bladder cancer and when there is a possibility of a recurrence. Pembrolizumab may be offered for bladder cancers that are not growing in the muscle walls of the bladder. Along with this, Nivolumab can be effective for people with invasive bladder cancer that has been removed using surgical methods but has a high chance of recurrence. 

2. Breast cancer – Pembrolizumab is a drug that is commonly used to treat breast cancers. This drug targets PD-1 protein blocks this protein and boosts the immune system thereby allowing it to take care of cancer cells. This drug can be used before and after surgery has been conducted and is useful for stage 2 and 3 cancers. It is also employed when cancer has recurred and it can’t be removed using surgery. This drug is administered through an IV infusion over a period of 3-6 weeks. 

3. Cervical Cancer – Cervical cancer is cancer of the cervix and occurs when the cells on the surface of your cervix transform into precancerous cells. Pembrolizumab is a drug that has shown promise when it comes to treating this type of cancer. This drug targets PD-L1, and attempts at boosting the immune responses of the body. If enough PD-L1 protein is detected in the body then Pembrolizumab can be used as a stand-alone form of treatment for cervical cancer that has come back or that has metastasized after availing traditional forms of treatment such as chemotherapy. 

4. Colorectal Cancer – Colorectal cancer refers to cancerous growth in part of the large intestine called the colon. The colon is the longest part of the large intestine. Checkpoint inhibitors have also proven highly effective against colorectal cancer. Pembrolizumab and Nivolumab have proven to be beneficial for colon cancer. Unlike Pembrolizumab which targets PD-L1 protein, Ipilimumab is a drug that blocks CTLA-4 protein and has proven to be effective against colorectal cancer. This drug is administered using an IV infusion over a span of 3-6 weeks. 

5. Liver Cancer – Liver Cancer is a type of cancer that occurs in the cells of your liver. When it comes to treating this type of cancer with the help of immunotherapy, checkpoint inhibitors have proven to be highly beneficial. Pembrolizumab and Nivolumab have shown positive results for various types of cancers and the same can be said for Liver cancer as well. Along with this, Ipilimumab in combination with Nivolumab can be used to treat liver cancer that has seen treatment already. This drug is given through IV infusion over a period of 3-4 weeks. 

Side Effects Of Checkpoint Inhibitors

Like any other form of treatment for cancer, patients experience certain side effects due to checkpoint inhibitors. Some of the most common side effects that are seen in patients when they avail this line of treatment include –

1. Diarrhea
2. Fatigue
3. Cough 
4. Nausea
5. Skin Rash
6. Loss of Appetite

Apart from these common side effects, in rare cases, a patient may experience some other serious side effects. It becomes important during such a situation that a patient lets their doctor know about these side effects so that they can then recommend a line of treatment that will suit their needs. Some serious side effects include –

1. Infusion reactions – Since these drugs are transmitted through an IV infusion a person may experience skin reactions and rashes. Infusion reactions can result in allergic problems, chills, rashes, fever, and even difficulty in breathing. If a patient is experiencing any of these symptoms after availing checkpoint inhibitors, then they should immediately try to contact their doctor since this may turn out to be something serious. 
2. Autoimmune reactions – In some cases, checkpoint inhibitors can result in autoimmune reactions. Since these drugs target a particular checkpoint protein, this then separates one of the safeguards from the body’s immune system. In some cases, the immune system may react to this removal by attacking other parts of the body, which can even lead to life-threatening situations. 

While in most cases the side effects of checkpoint inhibitors aren’t as serious as other modes of treatment, in certain cases a person may experience a series of severe side effects which should not be taken for granted no matter what. 

Summary 

Checkpoint Inhibitors have gained popularity over the last few years due to the various positive outcomes. Due to negligible side effects and the ease with which these drugs are administered, Checkpoint Inhibitors have garnered a reputation for becoming a viable option for cancer treatment.