Anti-CD19 CAR-T cells: Digging in the dark side of the golden therapy

The unprecedented technological advances in genetic engineering have resulted in the advent of the very promising chimeric antigen receptor (CAR)-T cell therapy. Based on the striking outcomes of clinical trials, the first two commercial CAR-T cell products, tisagenlecleucel and axicabtagene ciloleucel, have been approved in both the United States and Europe for the treatment of patients with highly aggressive CD19-positive hematological malignancies. Despite the initial remarkable responses many patients finally relapse, implying the presence of resistance mechanisms. In this review, we describe the limitations and resistance mechanisms to anti-CD19 CAR-T cells and address potential strategies to overcome CAR-T cell barriers.