CAR T-Cell Immunotherapy 

Breakthrough of the Year 2022

 

At the beginning of every year, the American Society of Clinical Oncology (ASCO) publishes a report on Clinical Advances in Oncology. This detailed report is published in the Journal of Clinical Oncology, the clinical oncology journal of the American Society of Clinical Oncology, and covers the major advances in cancer treatment in the past year, including prevention, treatment, and patient care and future approaches. Every year, leaders in the field of oncology also select one area of ​​research that has made the most progress to name it Breakthrough of the Year.

 

For the last 2 years, immunotherapy has been the breakthrough of the year. This groundbreaking change in the way cancer is treated has transformed care for many patients. In fact, the American Society of Clinical Oncology estimates that immune checkpoint inhibitors could save 250,000 years of life for American patients with advanced lung cancer who might be prescribed a checkpoint inhibitor. Immune checkpoint inhibitors are drugs that remove the brakes that constrain the body’s immune system and release it to fight cancer.

 

The latest Breakthrough of the Year is a new type of immunotherapy known as chimeric antigen receptor (CAR) T-cell therapy.

 

What is CAR-T Cell Immunotherapy?

When the immune system is working normally, immune cells circulate throughout the body looking for things that should not be present in the body, such as bacteria and viruses. These immune cells seek out invaders by using “receptors,” which can be thought of as antennas or sensors. When the receptors find invaders in the body, special immune cells spring into action to destroy them. These special cells are called cytotoxic T cells.

 

Unfortunately, cancer cells often have the ability to hide from being found by immune cells, which is why cancer cells can grow uncontrollably. Immunotherapy is a cancer treatment designed to make the body’s immune system capable of detecting and destroying cancer cells. Immune checkpoint inhibitors have been a successful approach in immunotherapy because they prompt the immune system to fight cancer at an accelerated rate.

 

However, CAR T cell therapy is different. It is a type of immunotherapy called “adoptive cell immunotherapy”. As described by ASCO President and Member Bruce E. Johnson, this technique allows physicians to genetically reprogram patients’ own immune cells to find and attack cancer cells throughout the body.”

 

In CAR T cell therapy, a person’s T cells are removed and taken to a laboratory. Genetic changes are made in T cells so that they attack cancer cells. These CAR T cells are grown in large numbers and then injected into the patient. One of the notable features of this treatment is that it is a “living therapy.” CAR T cells usually only need to be injected once as they continue to multiply in the body. CAR T cells continue to fight cancer in the patient’s body, and their effectiveness may even increase over time.

 

Chimeric antigen receptor (CAR) T-cell treatment changes the immune system to be more effective at finding and destroying cancer cells. The immune system is very complex and involves many different types of cells and systems throughout the body. One of these cells is called a lymphocyte, which is a type of white blood cell that works to fight infection. There are several types of lymphocytes, one of which is called a T-lymphocyte.

 

T-lymphocytes play an important role in CAR T-cell therapy by killing cancer cells and cells infected by a virus. Cancer cells often evade the body’s normal immune system, but CAR T-cell therapy helps to improve the ability of T cells to find and destroy cancer cells.

 

CAR T cell treatment works by causing the T cells to focus on a substance called an antigen that is found on the surface of cancer cells. In the manufacture of CAR T cells, a protein is added to the surface of the T cells that helps them target the cancer cells. This protein is called a chimeric antigen receptor, or CAR.

 

CAR T cell treatment causes the T cells to focus their attention on a substance that the body thinks is harmful, called an antigen, that is found on the surface of specific cancer cells. In the manufacture of CAR T cells, a protein is added to the surface of the T cells to help them achieve this approach. This protein is called a chimeric antigen receptor, or CAR. This CAR protein is actually made up of 3 other proteins: 1 protein that recognizes antigens on the cancer cell and 2 proteins that cause the T cell to activate when that first protein binds to an antigen on the cancer cell. When a T cell has an added CAR, it is called a “CAR T cell.” CAR T cells float around the body and seek out cells that carry the antigen programmed for the CAR protein, such as certain cancer cells.

 

When a CAR T cell comes into contact with an antigen from a cancer cell, it becomes activated. The CAR-activated T cells multiply and send signals to other parts of the immune system to come to the site of the cancer cell. These signaling proteins are called cytokines. All of these cytokines and activated T cells then cause significant inflammation focused on the cancer cell, leading to cancer cell death. If all the cancer cells die, the cancer may go into remission, which means the cancer is temporarily or permanently gone.

 

What Happens When a Cancer Patient is Treated With CAR-T Cell Immunotherapy?

First of all, a person with cancer should be referred to a specialized center for this type of treatment. Next, your T cells need to be collected. It’s important to know that T cells are often affected by previous cancer treatments and may not be as healthy because of those treatments. Ideally, the T cells should be as healthy as possible when CAR T cells are made.

This often means that a person’s T cell collection must be done during a break in treatment. This means that the doctor must carefully make sure that the cancer is not too active or causing too many symptoms while treatment is paused, so that as many healthy T cells as possible are collected. For some types of cancer, this is the most difficult part of the process, and some people may not be suitable for CAR T cell treatment because of it.

 

After a certain amount of time has passed without treatment, the T cells are collected through a process called apheresis. During apheresis, the person’s blood is circulated through a machine that filters out the T cells and returns the rest of the blood to the person. These cells are then sent to a manufacturer to be created into CAR T cells, a process that typically takes 3 to 6 weeks. During manufacturing, the person’s normal T cells are activated, multiply, and become infected with a virus, causing a genetic modification that adds the CAR to the T cell. The CAR T cells are frozen and shipped back to the person with the oncologist. While waiting for manufacturing to finish, the person’s usual cancer treatment can be resumed.

 

Before the doctor infuses the CAR T cells into the person with cancer, a short course of chemotherapy called lymphodepletion is given for 2 to 3 days so that the normal immune system does not think the CAR T cells are abnormal and reject them. The CAR T cells are then removed from the freezer, thawed, and infused through the blood, similar to a blood transfusion.

 

This is when the CAR T cells begin their activity. They circulate through the body looking for cancer cells, activating, multiplying, using cytokines for support, and killing the cancer.