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Lysis of MYCN-amplified neuroblastoma cells by MYCN peptide-specific cytotoxic T lymphocytes.
- Source :
-
Cancer research [Cancer Res] 2000 Apr 01; Vol. 60 (7), pp. 1908-13. - Publication Year :
- 2000
-
Abstract
- The effectiveness of cell-mediated immunotherapy for cancer can be limited by loss-of-antigen mutations that occur during tumor growth. In neuroblastoma, amplification of the MYCN oncogene correlates with rapid tumor progression and a poor prognosis overall. We propose that the MYCN protein, the high-level expression of which is required for maintenance of the malignant phenotype, would be an ideal target for vaccine therapy. The MYCN-derived S9K peptide (amino acids 7-15; STMPGMICK), which contains an HLA-A1 binding motif, was used to generate CTLs from the peripheral blood lymphocytes of an HLA-A1+ healthy donor and an HLA-A1+ patient with MYCN-amplified neuroblastoma These CTL lines specifically lysed HLA-matched, MYCN-amplified neuroblastoma tumor cells. They did not lyse either HLA-mismatched, MYCN-amplified, or matched/nonmatched, non-MYCN-amplified tumor cells. The CTL activity was inhibited by a monoclonal antibody to a class I HLA monomorphic determinant but not by one specific for HLA class II, consistent with a class I-restricted mechanism of cytotoxicity. Antibodies to CD8, but not those to CD4, also inhibited CTL activity, identifying CD8+ lymphocytes as the effector cell population. These results show that MYCN-derived peptides can serve as tumor-specific antigens and suggest a rational approach to cell-mediated immunotherapy for MYCN-amplified neuroblastoma.
- Subjects :
- Adult
Antibodies, Monoclonal pharmacology
Brain Neoplasms genetics
Brain Neoplasms pathology
Child
Cytotoxicity, Immunologic
Female
HLA-A1 Antigen immunology
Humans
Infant
Male
Neuroblastoma genetics
Neuroblastoma pathology
Tumor Cells, Cultured
Brain Neoplasms immunology
Gene Amplification
Genes, myc
Neuroblastoma immunology
Peptide Fragments toxicity
Proto-Oncogene Proteins c-myc chemistry
T-Lymphocytes, Cytotoxic immunology
Subjects
Details
- Language :
- English
- ISSN :
- 0008-5472
- Volume :
- 60
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Cancer research
- Publication Type :
- Academic Journal
- Accession number :
- 10766179