title: A genetically modified allogeneic cellular vaccine generates MHC class I-restricted cytotoxic responses against tumor-associated antigens and protects against CNS tumors in vivo.
abstract: An active immunotherapeutic strategy using transfected allogeneic cells for targeting the mutant epidermal growth factor receptor (EGFRvIII) on intracranial tumors was examined. Immunization with allogeneic 300.19/EGFRvIII cells induced CD8+ cytotoxic T-lymphocytes against EGFRvIII bearing syngeneic B16-F10 melanoma or 560 astrocytoma cells (H-2b), but not against allogeneic NR6 cells (H-2q) also bearing EGFRvIII significant NK cell activity was also noted in vitro. Vaccination protected against intracranial challenge with EGFRvIII-positive tumor, with 50% long term survival. In vivo depletions of effector cell subsets demonstrated the requirements for both CD8+ and CD4+ T-cells but not NK cells in producing this protective effect. These data demonstrate the generation of significant, antigen-specific and MHC class I-restricted cytotoxic immune responses which are effective against tumors present in the CNS.
authors.affiliation: Preuss Laboratory for Brain Tumor Research, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: D M
authors.initials: DM
authors.lastname: Ashley
authors.forename: J H
authors.initials: JH
authors.lastname: Sampson
authors.forename: G E
authors.initials: GE
authors.lastname: Archer
authors.forename: S K
authors.initials: SK
authors.lastname: Batra
authors.forename: D D
authors.initials: DD
authors.lastname: Bigner
authors.forename: L P
authors.initials: LP
authors.lastname: Hale
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology*; D019496:Cancer Vaccines / Q000276:immunology*; D016543:Central Nervous System Neoplasms / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D003602:Cytotoxicity, Immunologic; D066246:ErbB Receptors / Q000235:genetics / Q000276:immunology; D005260:Female; D005821:Genetic Techniques; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D007114:Immunization; D051379:Mice; D009154:Mutation; D009368:Neoplasm Transplantation; D016019:Survival Analysis; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D015395:Histocompatibility Antigens Class I; D066246:ErbB Receptors