One in five cancers affects blood cells and lymph nodes, causing leukemias and lymphomas, respectively. Although their treatment with drugs has led to a great advance in their cure, there are cases where there is no clinical response or resistance to them is generated. For a few years there has been an alternative for these cases: a cell therapy that collects the T-lymphocytes of these patients, modifies them through genetic engineering in the laboratory and they are again administered to the patient so that they more effectively attack the cancer. This innovative new cellular medicine, also called chimeric antigen receptor T-lymphocyte therapy (CAR-T), is not without problems that can be summarized in the appearance of side effects, cases that are insensitive to the therapy and its high economic cost. Therefore, it would be very important to be able to select which patients are likely to benefit from the use of CAR-T cells. Dr Esteller’s group decided to look in detail at the molecular characteristics of more than 100 samples of CAR-T cells provided to patients with leukemias and lymphomas. They discovered that there was a genetic regulation profile (epigenome) that was associated with the absence of disease relapse and an improved overall survival of these people. In addition, it was observed that this epigenetic pattern wass typical of young T lymphocytes that, as they have a long life ahead and a greater capacity to remain in the patient’s bloodstream, perhaps for this reason they are more efficient CAR-T cells. It is worth investigating now whether these cell subpopulations would be ideal to be selected and administered, or if they can be enriched using epigenetic drugs that are given in the context of other leukemias and lymphomas.
Institut de Recerca contra la Leucèmia Josep Carreras (IJC)
– Garcia-Prieto CA, Villanueva L, Bueno-Costa A, Davalos V, […], Besser MJ, Avigdor A, Jacoby E, Esteller M 2022, ‘Epigenetic Profiling and Response to CD19 Chimeric Antigen Receptor T-Cell Therapy in B-Cell Malignancies‘, Journal of the National Cancer Institute, 114, 3, 436-445.