Cancer cells are notorious for avoiding detection by the body’s immune system, which makes them difficult to treat. But a promising new type of genetically engineered T-cell that can effectively destroy solid cancer tumors may be just what the doctor ordered.
Killer T-cells are an important part of the immune response. They are the body’s security guards, actively patrolling for things that don’t belong, such as infections and other diseases. Killer T-cells have surface receptors that recognize and destroy foreign invaders and abnormal cells.
Cancer cells can escape detection by killer T-cells, making them difficult to destroy. But there is a way our body’s T-cells can be “taught” to recognize and attack cancer cells. One approach is to use chimeric antigen receptor (CAR) T-cells, genetically engineered cells with a new receptor that allows them to bind to and kill cancer cells.
Different cancers have different types of antigens, and each type of CAR T-cell immunotherapy is designed to fight a specific cancer antigen. CAR T-cells have been used to treat chronic lymphocytic leukemia (CLL) and non-Hodgkin lymphoma with success rates of 35% to 70%, but have been less successful in treating solid cancer tumors.
Now, researchers at the Peter MacCallum Cancer Center in Australia have tested the effectiveness of a new type of CAR T-cell in treating solid tumors.
“While CAR T-cell therapy has been approved in some types of blood cancers such as leukemia, lymphoma and myeloma, the success of CAR T-cells in solid cancers has been limited,” said Paul Neeson, a corresponding author of the study. “This is due to factors including poor CAR T-cell expansion, persistence and exhaustion when fighting tumors.”
The researchers used a young T-cell as a substitute, which was similar to a stem cell. Called T stem-like CAR T-cells, these cells carry the CAR receptor and have an increased ability to reproduce while persisting in the body for a long time. Testing with the new cells yielded promising results.
“Importantly, these T stem-like CAR T-cells showed improved anti-tumor function in culture dishes and in four pre-clinical models. In fact, they completely eradicated pre-existing solid tumors, when they were combined with the immune checkpoint drug, anti-PD-1,” Neeson said.
To distinguish normal cells from foreign ones, the immune system uses “checkpoint” proteins on immune cells that act like switches that need to be turned on or off to initiate an immune response. Monoclonal antibody drugs can be designed to target these checkpoint proteins, and although they do not kill cancer cells directly, they help the immune system to better attack cancer cells.
PD-1 is a checkpoint protein on T-cells that acts as an off-switch, preventing T-cells from attacking other cells in the body. Monoclonal antibodies that target PD-1 can block this binding (hence, anti-PD-1), boosting the body’s immune response against cancer cells.
The researchers can generate fully functional T stem-like CAR T-cells in six days instead of the standard 14 days, making the process both cost-effective and scalable.
They hope to test the next generation of CAR T-cells in clinical trials on pediatric patients with difficult-to-treat blood cancers before trying to treat other types of cancer.
“We will aim to use these cells in two pediatric leukemias that are resistant to treatment,” Neeson said. , Once we show that these cells are safe, we will turn our attention to developing this treatment for pediatric solid cancers, including osteosarcoma and neuroblastoma.”
Osteosarcoma (osteogenic sarcoma) is a type of bone cancer most often seen in the long bones of the arms and legs. It is common in teenagers and young adults. Neuroblastoma begins in immature nerve cells (neuroblasts) and can develop in different areas of the body. It occurs mostly in infants and children under five years of age.
The video below by the Peter McCallum Cancer Center explains how T-cells work as part of the body’s immune response and how CAR T-cells are produced.
CAR-T Cells: The Engineered Cancer Killer
The study was published in science translational medicine,
Source: Peter MacCallum Cancer Center