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A genetically modified allogeneic cellular vaccine generates MHC class I-restricted cytotoxic responses against tumor-associated antigens and protects against CNS tumors in vivo

journal contribution
posted on 1997-09-01, 00:00 authored by David Ashley, J H Sampson, G E Archer, S K Batra, D D Bigner, L P Hale
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.

History

Journal

Journal of neuroimmunology

Volume

78

Issue

1-2

Pagination

34 - 46

Publisher

Elsevier

Location

Amsterdam, The Netherlands

ISSN

0165-5728

Language

eng

Publication classification

C1.1 Refereed article in a scholarly journal

Copyright notice

1997, Elsevier Science B.V.