CAR-engineered T cells, or CAR-T cells, is a novel immunotherapy strategy to treat patients with hematologic diseases, and that has potential in the treatment of solid tumors.
Its efficacy has been proven in several clinical trials in which CAR-T cell therapies have achieved complete response rates of 50%-90% in hematologic cancers1. These very successful results have led to a revolution in cancer immunotherapy by intensifying the development of strategies extending the use of CAR-T cells to other hematologic malignancies and, in particular, to solid tumors.
What does it involve?
Lymphocytes are a type of blood cell responsible for the specific immune response of our body against foreign agents such as bacteria, viruses or tumor cells. There are 3 distinct types of lymphocytes: T cells responsible for cell response, antibody-producing B cells and natural killer (NK) cells that destroy infected cells.
CAR-T cells are essentially T cells from the patient, extracted from blood, which are modified in the laboratory and are reintroduced into the patient’s bloodstream. These cells are modified to express antigen receptors on and specific to cancer cells, so that once they are returned to the patient’s blood vessels, they can attack cancer cells rather than healthy cells.
How does the treatment work?
T cells are taken from the patient by a blood draw. They are then prepared in the laboratory for 10-15 days. Once they are ready, following a chemotherapy conditioning cycle, they will be infused back into the patient, so that the patient will have perpetual T cells loaded with “anti-cancer weapons” to fight the type of blood cancer he/she has.
Clinical trials with CAR-T cells
The first clinical trials using this therapy were conducted in 2016 in the United States, and they were highly successful. The results were spectacular and completely surprising for the world of medicine in general and hematology in particular. 80% of patients were disease free one year after undergoing CAR-T therapy. It is important to note that all of these patients were children or very young people, all under 25 years of age, who had not responded to any of the previous treatments, including blood stem cell transplants.
There are currently several clinical trials using this type of immunotherapy in Spain. Diseases such as B-type acute lymphoblastic leukemia, Hodgkin lymphoma, B-type non-Hodgkin lymphoma, T-type Hodgkin lymphoma, acute myeloid leukemia, and multiple myeloma have been successfully treated.
However, although trials in breast, ovarian, lung and prostate cancer and in mesothelioma and sarcomas are currently ongoing, a number of challenges still need to be addressed in the application of CAR-T in solid tumors.
Julia Tarrats, Bioquímica
1Labanieh, L., Majzner, R.G. & Mackall, C.L. Programming CAR-T cells to kill cancer. Nat Biomed Eng 2, 377–391 (2018). https://doi.org/10.1038/s41551-018-0235-9