CAR T Cells: Overview & Side Effects

Overview

Chimeric antigen receptors (CAR) T-cell therapy is a type of immunotherapy called “adoptive cell immunotherapy”.

Immunotherapy collects and uses patients’ own immune cells to treat their cancer. It improves the body’s ability to detect and kill cancer cells. The immune system is the body’s defense against infection and cancer. It is made up of billions of cells. Immunotherapy is based on the concept that immune cells or antibodies can recognize and kill cancer cells. Utilizing the immune system for advanced cancer treatment has shown remarkable potential in recent years. One of the most promising immunological approaches to fight cancer is CAR T cells.

CARs are engineered T cell receptors that redirect T cells to recognize and destroy cancer cell targets. The basic structure of a chimeric antigen receptor consists of ectodomain, transmembrane domain, and endodomain. In CAR T-cell therapy, a person’s T cells are removed and taken to a laboratory. The T cells will be genetically changed, so that they will attack cancer cells. These CAR T cells are grown in large numbers and then injected into the patient. CAR T cells are injected only once, because they will multiply in the body.

In 2017, two CAR T-cell therapies were approved by the Food and Drug Administration (FDA), one for the treatment of children with acute lymphoblastic leukemia (ALL) and the other for adults with advanced lymphomas.

Principles

T cells are collected from a patient. CAR T cell therapy requires the collection of T cells from the blood of the patient or donor.

T cells are reengineered in a laboratory. The T cells are sent to a laboratory and genetically engineered. DNA will be introduced into T cells to produce CARs on the surface of the T cells.

The reengineered CAR T cells are then multiplied. The reengineered T cells are then multiplied within the laboratory before being reinfused into the patient. The CAR T cells can further multiply within the body while destroying the targeted cancer cells that display the specific surface antigen.

The CAR T cells are thawed and then infused into the patient. Before the patients receive the infusion of CAR T cells, they are given a brief course of one or more chemotherapy agents, called “lymphodepletion”. In this way, CAR T cells return to the patient’s bloodstream and multiply in number.

The CAR T cells help guard against recurrence. CAR T cells can eliminate all the cancer cells and remain in the body months after the infusion is completed. The therapy will result in long-term remission for some types of blood cancer.

Risks

This new cancer treatment approach may be powerful and helpful. However, like all cancer therapies, CAR T-cell therapy can cause several side effects, which need to be considered.

  • Cytokine-Release Syndrome (CRS)

It is the most frequent side effect of CAR T-cell therapy. As part of the immune-related duties, T cells will release cytokines that are certain chemical messengers, helping the T cells carry out their functions. Cytokines are produced when the CAR T cells multiple in the body and kill the cancer cells. CRS may occur within 1 to 21 days of CAR T-cell infusion. CRS symptoms can range from mild flulike symptoms that include nausea, fatigue, headache, chills, fever, low blood pressure, tachycardia, capillary leakage, cardiac arrhythmias, cardiac failure, hemophagocytic and so on.

  • Neurologic Problems

CAR T-cell therapy can also contribute to neurologic toxicities, causing neurologic problems, including problems remembering words, difficulty speaking, being less alert, delirium, hallucinations, seizures, and coma. In most cases, the symptoms can be resolved over several days without intervention. However, there can be life-threatening adverse neurological events.

  • Anaphylaxis

It is a life-threatening allergic reaction. It is possible for a patient receiving CAR T-cell therapy to have an overwhelming immune response against the CAR itself. Symptoms of anaphylaxis include hives, facial swelling, low blood pressure and respiratory distress. Monitoring and immediate treatment of this life-threatening side effect are necessary and critical.

  • B-Cell Aplasia

CAR T-cell therapy targets antigens on the surface of B cells. However, it not only destroys cancerous B cells, but also normal B cells. Therefore, B cell aplasia, which is low numbers of B cells or absent B cells, is potential result of some CAR T-cell treatment and serves as a useful indicator of ongoing CAR T-cell activity. B-Cell Aplasia will lead to less ability to make the antibodies that protect against infection.

  • Tumor Lysis Syndrome (TLS)

It is another known side effect of CAR T-cell therapy. Tumor Lysis Syndrome is a group of metabolic complications which occur due to the breakdown of dying cells, usually at the onset of toxic cancer treatments. However, TLS may occur one month or more after CAR T-cell therapy. TLS cause organ damage and can be a life-threatening side effect.


Keywords: CAR T-cell therapy.

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* The Content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition.