Researchers at Tel Aviv University have developed a new form of chimeric antigen receptors (CAR) T-cell therapy that could be used to treat patients with solid tumors.
CAR T-cell therapy is a form of immunotherapy that can be highly effective at treating leukemia, a form of blood cancer. CAR T-cell therapy uses the body’s immune system to attack cancer cells. T-cells are a type of white blood cell (lymphocyte) that attack foreign cells, although they do not normally attack cancer cells.
The therapy involves harvesting T-cells from a patient with cancer and adding chimeric antigen receptors to the cells in the lab. The engineered cells are then reintroduced into the patient and they find the cancer cells, bind to antigens on their surface, and kill them.
This form of immunotherapy can be very effective and, in contrast to other forms of treatment for cancer, CAR T-cell therapy serves as a long-term treatment for cancer as the T-cells will continue to kill cancer cells. Other forms of cancer therapy are short-term treatment options. With chemotherapy, for example, it is only effective while the drugs are present in the body.
Even though a patient’s own cells are used in this treatment, there can still be side effects such as severe inflammation; however, the side effects are nowhere near as bad as chemotherapy. With chemotherapy, toxic chemicals are introduced into a patient which accumulate in fast-growing cells such as cancer cells and kill them. The side effects result from the high toxicity of the chemicals used to kill the cancer cells. They will also kill other types of fast-growing cells such as hair follicles and the cells lining the gastrointestinal tract. The side effects can include severe pain, nausea, hair loss, vomiting, nerve problems, muscle problems, and anemia.
Unfortunately, efforts to use CAR T-cell therapy to treat cancers that form solid tumors have not been nearly as successful. Until now.
Dr. Yaron Carmi and his team of researchers at Tel Aviv University Sackler Faculty of Medicine identified a specific type of T-cell that can be engineered to have greater specificity and will attack solid tumors with much higher efficiency.
“Our lab discovered a distinct subset of helper T cells, also known as CD4+ T cells, that express the high-affinity receptor for IgG [an antibody] and efficiently kill tumor cells coated with these antibodies,” said Dr. Carmi. “This method uses CAR T-cell therapy and combines it with antibody specificity. Based on this discovery we were able to engineer novel T cells with enhanced tumor-killing activity and higher specificity, compared with other T cell-based therapies for cancer.”
This new treatment could be used to treat cancers of all types. The treatment would be preferable to chemotherapy as the side effects are far less severe. Dr. Carmi and his team are now testing the new treatment in a preclinical study on mouse models of cancer as well as in human samples. Phase 1 clinical trials are expected to start within 3 years.
The study is detailed in the paper – A distinct subset of FcγRI-expressing Th1 cells exert antibody-mediated cytotoxic activity – which was recently published in the Journal of Clinical Investigation. DOI: 10.1172/JCI127590