Cancer cells are notorious for evading detection by the body’s immune system, making them difficult to treat. But her T cells, a promising new type of genetically engineered T cell that can effectively destroy solid-tumor tumors, may be just what doctors ordered.
Killer T cells are an important part of the immune response. They are the body’s guards, actively patrolling unrelated things such as infections and other diseases. have surface receptors that destroy them.
Cancer cells can evade detection by killer T cells, making them difficult to destroy. But there are ways to “teach” her T cells in our body to recognize and attack cancer cells. One approach is to use chimeric antigen receptor (CAR) T cells. These are genetically engineered cells with new receptors that allow 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 specific cancer antigens. CAR T cells have been used to treat chronic lymphocytic leukemia (CLL) and non-Hodgkin’s lymphoma with success rates of 35% to 70%, but have been less successful in treating solid tumors.
Researchers at the Peter MacCallum Cancer Center in Australia are now testing the efficacy of a new class of CAR T cells in treating solid tumors.
“CAR T-cell therapy has been approved for some types of hematologic cancers, including leukemia, lymphoma, and myeloma, but CAR T-cells have had limited success in solid tumors,” said the study’s authors. “This is due to factors such as insufficient CAR T cell proliferation, persistence, and fatigue in fighting tumors,” said author Paul Neeson.
The researchers instead used young T cells, which are more like stem cells. These cells, called T-stem-like CAR T cells, have enhanced regenerative capacity when they carry CAR receptors and persist for a long time in the body. Tests on new cells yielded promising results.
“Importantly, these T-stem-like CAR T cells improved anti-tumor function in culture dishes and in four preclinical models. solid tumors have been completely eradicated,” said Neeson.
To distinguish between normal and foreign cells, the immune system uses “checkpoint” proteins on immune cells. This protein acts like a switch that must be turned on or off to initiate an immune response. Monoclonal antibody drugs can be designed to target these checkpoint proteins, and while they won’t kill cancer cells directly, they can help the immune system 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) and boost the body’s immune response against cancer cells.
The researchers were able to generate fully functional T-stem-like CAR T cells in 6 days instead of the standard 14 days, making the procedure both cost-effective and scalable.
They want to try next-generation CAR T cells in clinical trials for pediatric patients with difficult-to-treat blood cancers before treating other types of cancer.
“We aim to use these cells in two treatment-resistant childhood leukemias,” said Neeson. We believe in harmonizing our cell products.. Once we have shown that these cells are safe, we will turn our attention to developing this treatment for solid tumors in childhood, including osteosarcoma and neuroblastoma. .”
Osteosarcoma (osteogenic sarcoma) is a type of bone cancer that is common in the long bones of the arms and legs. It is commonly seen in teenagers and young adults. Neuroblastoma arises from immature nerve cells (neuroblasts) and can occur in many different areas of the body. It is most commonly seen in infants and children under the age of 5.
The video below by Peter MacCallum Cancer Center explains how T cells function as part of the body’s immune response and how CAR T cells are generated.
CAR-T cells: engineered cancer killers
This research Science Translational Medicine.
Source: Peter McCallum Cancer Center
