Chimeric Antigen Receptor-T Cells Fate after Infusion: Cellular Kinetics and Molecular Monitoring

Chimeric antigen receptor (CAR) T cells are considered human gene therapy products in which T lymphocytes are genetically modified to recognize a specific target antigen for therapeutic purposes. CAR-T cell therapy has shown particular success in the treatment of hematological neoplasms and, to date, the FDA has approved six commercial products for the treatment of relapsed/refractory B-cell malignancies. Because CAR-T cell therapy is associated with considerable toxicities, mainly cytokine release syndrome and neurological toxicity, it is reserved for patients with advanced-stage disease who have not responded to previous therapies and have no other treatment options. However, the efficacy of CAR-T cell therapy is highly variable, and approximately 30% to 50% of treated patients experience relapse after administration. Several variables, including the type of CAR construct, manufacturing procedure, infusion volume, quality of the manipulated T cells, and the patient’s tumor burden, may influence the fate and efficacy of CAR-T cells. In this review, specific attention is focused on molecular monitoring after infusion and on the potential occurrence of uncontrolled events, such as insertional mutagenesis, clonal T-cell expansion, or the onset of secondary T-cell lymphomas.