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Dr. Joshua Mansour is a board certified hematologist and oncologist with additional training at Stanford in cell therapy and bone marrow transplantation. In our talk, he focuses on the innovations and progress in CAR T cell therapy while also discussing cell therapy as a whole, the difference between cell therapy and CAR T cell therapy, the steps of CAR T cell therapy, and more details about this form of cancer treatment.
What is cell therapy?
The simple definition of cell therapy is a treatment in which cells are transfused or injected into a patient to cause a specific response. This is a broad field of study that can include different cell treatments, including transplantation of the patient’s own cells, transplantation of donor cells, and CAR T cell therapy.
CAR T cell therapy has been around for over 20 years now and is a type of immunotherapy that helps T cells recognize cancerous cells in the body and attack them. It can be described as a “lock and key method” because it works through specificity.
How does CAR T cell therapy work?
In this treatment, blood is removed from the patient, which T cells are extracted from. They are then given to a lab where a Chimeric Antigen Receptor (CAR) is attached to the cells, and are given time to multiply in the lab. Then, the CAR T cells are infused back into the patient with the new receptor protein, which is able to recognize and attack cancer cells.
Who is eligible for CAR T cell therapy?
Not every patient can undergo CAR T cell therapy. Some factors that have to be looked at prior to treatment are:
- The patient’s blood counts
- The relative disease stability of the patient
- The patient’s ability to tolerate toxicity
What are potential side effects to this treatment?
One side effect that is almost always expected to some extent is cytokine release syndrome. This usually starts from day 1-3 of treatment and continues for several days. Cytokine release syndrome can have various symptoms, the most common ones being fevers, shortness of breath, fatigue, nausea, vomiting, and diarrhea.
Another common side effect is neurotoxicity, which usually starts on day 3-5 of treatment and ends around day 5-8. Patients will be asked to answer a set of questions 2-3 times a day in the early stages of treatment to detect signs of neurotoxicity and treat it as soon as possible.
What is the process and experience like for the patient?
Patients will first have their blood removed and sent to a lab. While they wait for the CAR T cells to be ready, patients undergo low-dose chemotherapy treatment to manage their cancer and suppress the patient’s microenvironment. Once the CAR T cells are ready, they are injected into the patient.
Dr. Mansour typically tells his patients to expect to be in the hospital for 2-3 weeks total for the treatment including the low-dose chemotherapy. Patients will often experience fatigue and other side effects after infusion which can last for as little as a few days of as long as a few months.
After being released from the hospital, patients will be given antiviral and antibacterial therapy because parts of their immune system will be subdued from treatment.
Where are we today with CAR T cell therapy?
Today, there are several CAR T cell therapies that are FDA approved, but patients will typically only use them if they have already exhausted all other traditional therapies. All of the current approved therapies relate to liquid tumors, but solid tumor CAR T cell therapy is currently on the rise with several clinical trials.
There are currently many ongoing CAR T cell therapy clinical trials for various cancer types, and Dr. Mansour urged patients to check the Trialjectory website and other resources to see if there were any available trials for their cancer type.
In today’s world, the COVID-19 pandemic is a crucial topic of discussion for any treatment. Patients undergoing CAR T cell therapy are more vulnerable to infections as a whole, which includes COVID, but this is true for other cancer treatments as well. Patients can still get this therapy if they have already received the COVID vaccine. However, because of the way the immune system reacts to CAR T cell therapy, Dr. Mansour generally tells his patient to wait about 100 days after treatment to get the COVID vaccine if they have not gotten it already.
Where is the future of CAR T cell therapy headed?
Researchers are looking to make several improvements to CAR T cell therapy in the future. For one, they are working to make chemotherapy an out-patient process to minimize time spent at the hospital. Another important goal is to try and make this treatment safer to patients by decreasing side effects.
On the technical side of the treatment, researchers are trying to increase the targets and proteins for this treatment. They are also looking to make more progress into solid tumors and solve problems relating to penetration of the tumor, which has been a significant challenge thus far.