Major histocompatibility complex-restricted lysis of neuroblastoma cells by autologous cytotoxic T lymphocytes.
Vigorous host immune reactivity to neuroblastoma may correlate with better prognosis, but identification of human cytotoxic T-lymphocyte (CTL) responses has been relatively unsuccessful. We generated neuroblastoma-reactive CTL lines from two human leukocyte antigen (HLA) A2+ neuroblastoma patients by stimulation of peripheral blood lymphocytes (PBLs) with irradiated autologous tumor cells pretreated with interferon-gamma in the presence of low concentrations of interleukin-2 (5 U/mL). These lines lyse autologous tumor cells but do not kill HLA mismatched allogeneic tumor cells, Epstein-Barr virus-transformed autologous B cells, or standard natural killer cell targets. Cytotoxic T lymphocytes generated from one patient recognize tumor cells from several HLA-A2 matched children, although the other patient's CTLs do not kill tumor cells from other HLA-A2+ individuals. Pretreatment of CTLs or target cells with appropriate standard monoclonal antibodies demonstrates that these CTLs are major histocompatibility complex class I (HLA-A2) restricted and that the effector cell population is CD8+. Our findings suggest that these tumor cells express at least one common HLA-A2 restricted antigen and at least one unique private epitope. Autologous tumor-specific CTLs can be readily generated from patients' PBLs and maintained in long-term culture using standard techniques.
Sarkar
A K
AK
DeBakey Department of Surgery, Baylor College of Medicine, and The Texas Children's Cancer Center, Texas Children's Hospital, Houston, USA.
Burlingame
S M
SM
Zang
Y Q
YQ
Dulai
V
V
Hicks
M J
MJ
Strother
D R
DR
Nuchtern
J G
JG
D000951:Antigens, Neoplasm / Q000276:immunology; D002460:Cell Line; D002648:Child; D002675:Child, Preschool; D000939:Epitopes; D005260:Female; D015789:HLA-A2 Antigen / Q000276:immunology*; D006801:Humans; D007223:Infant; D008297:Male; D009447:Neuroblastoma / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014407:Tumor Cells, Cultured
D000951:Antigens, Neoplasm; D000939:Epitopes; D015789:HLA-A2 Antigen