A genetically modified allogeneic cellular vaccine generates MHC class I-restricted cytotoxic responses against tumor-associated antigens and protects against CNS tumors in vivo.
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.
Ashley
D M
DM
Preuss Laboratory for Brain Tumor Research, Duke University Medical Center, Durham, NC 27710, USA.
Sampson
J H
JH
Archer
G E
GE
Batra
S K
SK
Bigner
D D
DD
Hale
L P
LP
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
D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D015395:Histocompatibility Antigens Class I; D066246:ErbB Receptors