Chimeric Antigen Receptor (CAR) T-Cell Therapy: What Does “Chimeric” Mean?

One of the most exciting new cancer treatments, CAR T-cell therapy takes its complicated name, in part, from a fire-breathing monster in an ancient Greek myth.

CAR is an acronym for “chimeric antigen receptor,” referring to genetically engineered molecules manufactured in a laboratory, inserted into the genetic material of immune T cells that have been removed from the patient’s body, and then expressed as proteins on the T-cell surface. The CARs are designed to give these T cells, a type of white blood cell, highly specific homing abilities so that when they are returned to the patient, the T cells can more easily recognize and attack cancer cells throughout the body.

CAR T-cell therapy
How CAR T-cell therapy works.

An antigen receptor recognizes and binds to a specific antigen – a protein like an allergen, a piece of virus, or a cancer-associated protein that can provoke an immune response. So what is a “chimeric” antigen receptor? The term “chimeric” – pronounced kih-MAIR-ik – means having the properties of a chimera, something that is made up of very disparate parts.

In Greek mythology, the Chimera was a monster comprising parts of different animals, usually depicted as a combination of a lion, a goat, and a serpent. In biology, a chimera can mean an organism composed of genetically different cells, or a hybrid protein made by splicing several different pieces of genetic code together.

The term chimeric has been given to the genetically engineered antigen receptors because they are artificial – not because they are dangerous.

In the CAR T cells currently in clinical use, this typically means that the genetic code for an antibody (a normal immune system defense mechanism) is spliced directly to two different molecules that help a T cell turn on and exert killing activity towards whatever that antibody recognizes.  In our natural immune system, these three pieces of immune machinery are in different locations on immune cells and not directly connected in a series for optimal efficiency of recognition and signaling, as they are in the CAR T cells.

At the present time, each batch of CAR T cells is tailor-made for each individual patient, using his or her T cells collected and separated from the bloodstream.

CAR T-cell therapy has proven to have dramatic benefits for some patients with advanced cancers, mainly leukemias and lymphomas. One such therapy, known as Yescarta, was approved in 2017 for some forms of aggressive, refractory non-Hodgkin lymphoma and is being used in the Cellular Therapies Program at Dana-Farber/Brigham and Women’s Cancer Center. Also approved by the FDA in 2017 was Novartis’s Kymriah for pediatric patients up to age 25 with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL). Kymriah is offered at Dana-Farber/Boston Children’s Cancer and Blood Disorders Center.

As of May 2018, CAR T-cell therapy has been approved by the U.S. Food and Drug Administration as standard therapy for some adult patients with aggressive non-Hodgkin lymphoma that has relapsed after prior treatments, or has not responded to other therapies (refractory), and for patients age 25 and under with relapsed or refractory  B-cell acute lymphoblastic leukemia.