Treatment > Gene Therapy

Meeting Abstract

Induction of CD4 And CD8 T Cells to the Tumor-Specific Antigen EGFRvIII

Gary Archer, Darell Bigner, Allan Friedman, Henry Friedman, Amy Heimberger, and John Sampson

Duke University, Durham, North Carolina, USA

The goals of this study were to determine whether DCs could be generated ex vivo from patients with malignant gliomas as defined by phenotypic and functional characteristics and to assess their ability to process and present the tumor-specific antigen EGFRvIII (epidermal growth factor receptor variant III).
The in-frame EGFRvIII deletion combines distant parts of the molecule, producing a novel glycine at the fusion junction.
This novel sequence is represented by the peptide PEP-3.
We first compared DCs generated from patients with malignant gliomas with a control group of patients undergoing craniotomy for nonneoplastic conditions.
Both groups were negative for lineage markers and had a high expression of both Class I and II antigens and the DC monocyte marker CD11c.
DCs generated from both groups were equal in generating a mixed lymphocyte reaction and in processing and presenting the common tumor-associated antigen carcinoembryonic antigen.
Autologous T cells were stimulated in vitro with DCs loaded with PEP-3 to induce EGFRvIII-antigen-specific CTLs.
These CTLs were able to lyse target DCs loaded with PEP-3 but not DCs loaded with a nonspecific peptide.
Both CD4 and CD8 T cells were shown to produce IFN-γ by ELISPOT in response to PEP-3.
DCs from patients with malignant gliomas are phenotypically and functionally normal and are capable of generating an immune response to a tumor-specific antigen that is relevant in patients with gliomas.

Copyright © 2003 by the Society for Neuro-Oncology