title: Achieving graft-versus-tumor effect in brain tumor patients: from autologous progenitor cell transplant to active immunotherapy.
abstract: Success in treating aggressive brain tumors like glioblastoma multiforme and medulloblastoma remains challenging, in part because these malignancies overcome CNS immune surveillance. New insights into brain tumor immunology have led to a rational development of immunotherapeutic strategies, including cytotoxic Tlymphocyte therapies and dendritic cell vaccines. However, these therapies are most effective when applied in a setting of minimal residual disease, so require prior use of standard cytotoxic therapies or cytoreduction by surgery. Myeloablative chemotherapy with autologous hematopoietic cell transplantation (autoHCT) can offer a platform upon which different cellular therapies can be effectively instituted. Specifically, this approach provides an inherent 'chemical debulking' through high-dose chemotherapy and a graft-versus-tumor effect through an autologous T-cell replete graft. Furthermore, autoHCT may be beneficial in 'resetting' the body's immune system, potentially 'breaking' tumor tolerance, and in providing a 'boost' of immune effector cells (NK cells or cytotoxic T lymphocytes), which could augment desired anti-tumor effects. As literature on the use of autoHCT in brain tumors is scarce, aspects of immunotherapies applied in non-CNS malignancies are reviewed as potential therapies that could be used in conjunction with autoHCT to eradicate brain tumors.
authors.affiliation: Department of Pediatrics, Hematology/Oncology, Rainbow Babies & Children's Hospital, Case Western Reserve University, 11100 Euclid Avenue, Mailstop 6054, Cleveland, OH 44106, USA. agne.petrosiute2@uhhospitals.org
authors.forename: Agne
authors.initials: A
authors.lastname: Petrosiute
authors.forename: Jeffery J
authors.initials: JJ
authors.lastname: Auletta
authors.forename: Hillard M
authors.initials: HM
authors.lastname: Lazarus
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000276:immunology / Q000628:therapy*; D019496:Cancer Vaccines / Q000627:therapeutic use*; D005909:Glioblastoma / Q000276:immunology / Q000628:therapy*; D020350:Graft vs Tumor Effect / Q000276:immunology*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007111:Immunity, Cellular; D016233:Immunotherapy, Active / Q000379:methods*; D008527:Medulloblastoma / Q000276:immunology / Q000628:therapy*; D014182:Transplantation, Autologous; D019139:Tumor Escape
chemical_list: D019496:Cancer Vaccines