A fun (but scary) fact: 1 out of 2 people will get cancer within their lifetime. Isn’t that insane? And yet… no cure is 100% effective. This deadly disease takes almost 9.6 million lives. Every. Single. Year.
We’ve been trying to cure cancer using our immune system since the 19th century, but in recent years we’ve been getting extremely close. In fact, we’re learning more and more about how we can manipulate immune cells so that they act as therapeutic agents (treatment) for cancer, and the science that supports immunotherapy treatments is stronger than ever.
The big question: Why doesn’t our immune system fight and kill cancer already?
It does! Yes, that’s right. Our immune system works to kill cancer in our bodies already.
Our cells mutate, and when they do become cancerous, and they’re individual, our immune system can tackle and kill them. If it didn’t we’d be getting cancer way more often than we do right now.
The problem arises when the growth of the cancerous tumor exceeds or matches the growth of the immune system.
You can think of the imbalance of power by comparing it to 1 person (immune cell) vs 4 criminals (cancerous cells). Who’s going to win? Probably the criminals, because there are more of them.
How do immune cells recognize invaders?
Another issue that immune cells face once the activity of the tumor is greater than that of the immune system is its ability to target and identify which cells are cancerous.
It does this by latching on and analyzing molecules on the cells’ surface, to detect whether or not the cell is part of your body. If the foreign cell that the immune cell has latched onto is not part of the body, it will turn on and release toxic chemicals (cytotoxicity) that will kill the invading cell. This can be done through methods that don’t involve the foreign cell exploding, and instead as a safe self-destruct method.
If the cell/substance is not part of your body, it is called an antigen. Antigens tend to trigger antibodies, which are used to neutralize the foreign substance.
There are 2 categories that the immune system can be divided into. Innate and adaptive.
Innate immunity is the nonspecific defense mechanisms that react relatively quickly once an antigen is introduced to the body. The innate immune response is activated by the chemical properties of the antigen.
- Chemicals in the blood
- Immune system cells that attack foreign cells in the body
Adaptive immunity is an antigen-specific immune response. This involves a two-step procedure:
- The antigen must first be processed and identified
- Once it has been recognized, the adaptive immune system creates a mass group of immune cells specifically designed to target that one antigen.
The adaptive immunity response includes a “memory” so that it can make future responses against a specific antigen much more efficient.
The “escape phase”
Here’s where our problem comes in. If not eliminated, cancer cells can develop genetic characteristics that help them escape from the detection of the immune system. This is called the “escape phase” and allows the cancer cell to lose the molecules on its surface that would otherwise reveal it to the immune cell.
The good news is that we’re working on editing the immune system so that it’s able to recognize and destroy the cancerous cells, even once they’ve reached the “escape phase”.
We can do this using cellular receptors. The DNA of immune cells is being programmed so that they act as response agents. This means that they follow an autonomous process to sense and then treat cancer.
What even are cellular receptors?
The receptors are embedded in the membrane of the cell. Think of the membrane as if it’s a fence around the cell and the receptors like security cameras on the fence.
There are 3 parts to the system.
- There’s the sensor that can be programmed to detect pathogenic signals (signals from an outside environment) or a certain microenvironment.
- The engineered cell then goes through a decision-making circuit to decide whether or not the cell that has been detected needs to be destroyed.
- Finally, it outputs the corresponding response (ie. if it decides that a cell is cancerous, it kills it).
Some inputs that a cell could be engineered to respond to include: antigens, the microenvironment, and different signals.
The main outputs that the engineered immune cell reacts to the input with could come in the form of: killing the other cell, producing antibodies and communicating with the immune system.
Inputs sense the disease. Outputs treat the disease.
Let’s take a deeper look at which immune cell we can engineer to achieve our desired output. Killing the cancerous cells.
The CAR T-cell clinical trial
T-cells have been a huge focus is cell therapies as they have the ability to exhibit cytotoxicity which can be targeted towards killing cancer cells. In addition to why T-cells are the perfect candidate for being engineered, they divide and expand throughout the body relatively quickly, and they’re easily obtainable from peripheral blood (the flowing/circulating blood). I mean, what’s not to like?
Our bodies already have T-cells that are able to recognize mutations in cancer.
Several strategies are being explored to engineer T-cells that go through a more extensive decision-making circuit when deciding whether or not a cell is toxic.
These strategies include dual-CAR targeting where T-cells are modified so that they now have a special receptor called Chimeric Antigen Receptors (CAR). The CAR’s prompt the T-cells to latch onto specific antigens, and then signal the T-cells to kill those cancerous cells.
In the above image, the orange receptors (CARs) have been added onto the T-cell, so that it can attack the cancerous cells.
Creation of CAR T-stem cells
Lab technicians would collect a sample of a patient’s T-cells from their blood, and then modify them by adding DNA (using an inactive virus) into them so that they would produce CARs on the surface.
The final step involves allowing the CAR T-cells to multiply, and when they are infused back into the patients.
When using CAR T-cells to target and treat cancer, it was observed that patients experienced a full recovery rate of up to 92% in Acute Lymphocytic Leukemia (cancer of the bone and bone marrow).
Despite these amazing results in cancers of the bone, we’re currently working on overcoming the barriers that transferring the usage of CAR T-cells to solid tumors holds, such as CAR T-cell expansion.
The innovation is insane and we’re looking at so many ways to solve the epidemic of cancer through “hacking” our very own immune system.
- Our bodies already fight cancerous cells, but cancerous cells become undetectable to the immune system once they reach the “escape phase” and lose all of their identification molecules.
- There are 2 categories of the immune system: Innate (nonspecific defense mechanisms) and Adaptive (specific design of an immune cell to target one type of antigen)
- CAR T-cells work as receptors by using a sensor to detect signals and then releasing an output based on the signal that it received
- Clinical trials have proven that CAR T-cells can be successful at eliminating the cancer of bone, and bone marrow.