Less is more: lymphodepletion followed by hematopoietic stem cell transplant augments adoptive T-cell-based anti-tumor immunotherapy

Adoptive T-cell immunotherapy combined with nonmyeloablative lymphodepletion has emerged as the most effective immunotherapy treatment for patients with metastatic melanoma (objective response rates of 50%). The mechanisms underlying this major advance in the field of immunotherapy include the elimination of regulatory elements and increased access to activating cytokines. This results in the activation of low-affinity T cells, enabling them to destroy tumors. We propose that a more complete depletion of the patient's immune system followed by transplantation with hematopoietic stem cells, which can be genetically modified, would be more effective in the treatment of metastatic cancer.