Rethinking lymphodepleting preconditioning in adoptive T cell therapy for durable tumor control

Adoptive T cell therapy (ACT) has transformed the treatment of several hematologic malignancies, yet patients may develop resistance and disease come back. Moreover, durable responses in solid tumors remain by far challenging. A central goal in the field has been to improve the engraftment, expansion, and persistence of the infused T cells. For this reason, non-myeloablative lymphodepleting chemotherapy is incorporated into most ACT protocols to create “space” and cytokine availability for transferred cells by removing competing immune cells.