title: Soluble CD70: a novel immunotherapeutic agent for experimental glioblastoma.
abstract: OBJECTIVE
  Given the overall poor outcome with current treatment strategies in malignant gliomas, immunotherapy has been considered a promising experimental approach to glioblastoma for more than 2 decades. A cell surface molecule, CD70, may induce potent antitumor immune responses via activation of the costimulatory receptor CD27 expressed on immune effector cells. There is evidence that a soluble form of CD70 (sCD70) may exhibit biological activity, too. A soluble costimulatory ligand is attractive because it may facilitate immune activation and may achieve a superior tissue distribution.
  
  
  METHODS
  To test the antiglioma effect of sCD70, the authors genetically modified SMA-560 mouse glioma cells to secrete the extracellular domain of CD70. They assessed the immunogenicity of the transfected cells in cocultures with immune effector cells by the determination of immune cell proliferation and the release of interferon-gamma. Syngeneic VM/Dk mice were implanted orthotopically with control or sCD70-releasing glioma cells to determine a survival benefit mediated by sCD70. Depletion studies were performed to identify the cellular mediators of prolonged survival of sCD70-releasing glioma-bearing mice.
  
  
  RESULTS
  The authors found that ectopic expression of sCD70 enhanced the proliferation and interferon-gamma release of syngeneic splenocytes in vitro. More importantly, sCD70 prolonged the survival of syngeneic VM/Dk mice bearing intracranial SMA-560 gliomas. The survival rate at 60 days increased from 5 to 45%. Antibody-mediated depletion of CD8-positive T cells abrogates the survival advantage conferred by sCD70.
  
  
  CONCLUSIONS
  These data suggest that sCD70 is a potent stimulator of antiglioma immune responses that depend critically on CD8-positive T cells. Soluble CD70 could be a powerful adjuvant for future immunotherapy trials for glioblastoma.
authors: Department of Neurosurgery, Indiana University, Indianapolis, Indiana, USA.
authors: James
authors: J
authors: Miller
authors: Guenter
authors: G
authors: Eisele
authors: Ghazaleh
authors: G
authors: Tabatabai
authors: Steffen
authors: S
authors: Aulwurm
authors: Gabriele
authors: G
authors: von Kürthy
authors: Lothar
authors: L
authors: Stitz
authors: Patrick
authors: P
authors: Roth
authors: Michael
authors: M
authors: Weller
mesh_terms: D000818:Animals; D001254:Astrocytoma / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D001932:Brain Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D053282:CD27 Ligand / Q000276:immunology* / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D002455:Cell Division / Q000502:physiology; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D007167:Immunotherapy / Q000379:methods*; D007371:Interferon-gamma / Q000378:metabolism; D008212:Lymphocyte Depletion; D051379:Mice; D008815:Mice, Inbred Strains; D009361:Neoplasm Invasiveness / Q000473:pathology; D012995:Solubility; D013154:Spleen / Q000166:cytology / Q000276:immunology; D015996:Survival Rate; D014162:Transfection
chemical_list: D053282:CD27 Ligand; D007371:Interferon-gamma