By Holly Alyssa MacCormick 

The human body is remarkably adept at defending itself from harmful cells and foreign substances, but sometimes it needs a little help. One way that scientists boost the immune system is through a form of genetic engineering known as chimeric antigen receptor, or CAR T-cell therapy. This therapy is currently used to treat certain cancers, but it may soon be used to treat other diseases as well.

The biology behind CAR T-cell therapy 

T-cells are a special type of immune cell that works as a sentinel in the body, constantly scanning for threats. CAR T-cell therapy helps the body’s own immune system work more effectively by genetically modifying T-cells so they can scan neighboring cells with greater accuracy.   

T-cells are formed in bone marrow and travel through the bloodstream and lymph system, scouring the surface of every cell they encounter.  They come in various shapes with different cell coatings made of bits of protein (called antigens) that dot the surface like toppings packed on the outside of an iced donut hole. The different shapes of those antigens help T-cells identify harmful cells through a kind of “lock and key” recognition system. 

T-cells have receptor “keyholes” that lock in with antigen “keys” on harmful cells. Cells studded with “familiar” antigens are considered friendly by T-cell receptors and are allowed to go on their way. But cells with antigens that T-cell receptors are programmed to read as harmful are actively bound by the T-cell and killed with chemicals released by the modified T-cell.  

How CAR T-cell therapy works 

CAR T-cell therapy functions like a “living drug,” reprogramming key cells in the body’s immune system to target disease with a one-time treatment. Creating these personalized therapies involves drawing some blood from a patient to get a sample of their T-cells. Once the T-cells have been separated from the other cells in the blood, they are mixed with an inactivated virus that has been repurposed to carry the genetic instructions for the engineered keyhole (the chimeric antigen receptor or CAR), the researchers want the T-cells to grow.  

With this genetic modification, the CAR T-cells can now recognize and lock onto a specific harmful cell type, such as cells of a patient’s specific kind of cancer.  

To make CAR T-cell therapy work as efficiently as possible, millions of copies of these engineered cells are grown in a laboratory, and then administered back to the patient intravenously. 

Once inside the body, the CAR T-cell-modified cells scan the neighboring cells they encounter in the bloodstream. When a modified CAR T-cell recognizes a foreign, harmful cell, it targets it for destruction by the patient’s own immune system. Once a targeted cell is killed, the modified CAR T-cell moves on unscathed, continuing the hunt until no harmful cells remain to kill. 

CAR T-cell therapy at CIRM 

CAR T-cell therapy was developed in the 1980s with the aim of treating HIV. Those early efforts were unsuccessful, but the therapy showed promise as a way to treat cancer. In 2017, the FDA approved the first CAR T-cell therapy to treat a form of childhood leukemia. Scientists are exploring how this therapy can be used to treat other cancers and diseases.   

CAR T-cell therapies currently focus on blood cancers, including multiple myeloma, leukemia, and non-Hodgkin lymphomas. This is in part because T-cells float in the blood. T-cells can also travel easily in the body’s blood and lymph system to target these cancers. T-cells work in other areas of the body too. However, solid tumors are trickier targets because of the dense tissue barrier. Tumors can have multiple (rather than single) proteins to target. Also, they can send out signals that inactivate nearby immune cells. 

The California Institute for Regenerative Medicine (CIRM) has funded research on CAR T-cell therapy for leukemia. The agency has also supported CAR T-cell research to treat other blood cancers, as well as autoimmune diseases, HIV, and aggressive brain cancers that affect children. 

There are currently 14 CIRM-funded clinical trials using CAR T-cell therapy. The agency supports or has supported dozens of research grants that are investigating ways to innovate and expand the use of CAR T-cell therapy. These studies include a small, early-stage clinical trial led by Steven G. Deeks, MD, that could pave the way for a potential one-shot cure for HIV; a study that’s investigating a CAR T-cell therapy to treat the most common type of kidney cancer; and a study that’s exploring use of CAR T-cell therapy for Systemic Lupus Erythematosus, a debilitating autoimmune disease.