Less is more: lymphodepletion followed by hematopoietic stem cell transplant augments adoptive T-cell-based anti-tumor immunotherapy.
Adoptive T-cell immunotherapy combined with non-myeloablative 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.
Wrzesinski
Claudia
C
National Cancer Institute, National Institutes of health, Clinical Research Center, Room 3-5816, 10 Center Drive, Bethesda, MD 20892-1201, USA. wrzesinc@mail.nih.gov
Restifo
Nicholas P
NP
D000818:Animals; D049109:Cell Proliferation; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D016219:Immunotherapy, Adoptive; D008213:Lymphocyte Activation / Q000276:immunology; D008231:Lymphopenia / Q000276:immunology / Q000628:therapy; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D011948:Receptors, Antigen, T-Cell