MYCN as a target for cancer immunotherapy.
MYCN is a potential target for cancer immunotherapy by virtue of its overexpression in numerous human malignancies and its functional role in tumour progression. Here we show limited expression of MYCN in normal human tissues indicating that anti-MYCN immune responses are unlikely to cross react with self tissues. An HLA-A2 restricted ten amino acid peptide epitope from MYCN, VILKKATEYV, was used to stimulate cytotoxic T cell lines from the peripheral blood of normal blood donors, and from a patient with MYCN amplified neuroblastoma. Strong and specific activity was seen against each MYCN overexpressing cell line and against autologous tumour cells. We generated two CTL clones capable of killing cells pulsed with as low as 0.5 nM of VIL peptide. Therefore strong and specific immune responses against MYCN expressing tumours are possible in patients with the most common HLA class 1 type in the Caucasian population.
Himoudi
Nourredine
N
Unit of Molecular Haematology and Cancer Biology, Institute of Child Health, WC1N 1EH, London, UK.
Yan
Mengyong
M
Papanastasiou
Antigoni
A
Anderson
John
J
D002460:Cell Line; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D015789:HLA-A2 Antigen / Q000276:immunology; D006801:Humans; D015151:Immunoblotting; D007167:Immunotherapy / Q000379:methods*; D000071447:N-Myc Proto-Oncogene Protein; D009369:Neoplasms / Q000276:immunology* / Q000628:therapy*; D009447:Neuroblastoma / Q000276:immunology; D009687:Nuclear Proteins / Q000276:immunology*; D015513:Oncogene Proteins / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014162:Transfection
D018984:Epitopes, T-Lymphocyte; D015789:HLA-A2 Antigen; C459801:MYCN protein, human; D000071447:N-Myc Proto-Oncogene Protein; D009687:Nuclear Proteins; D015513:Oncogene Proteins