TY - JOUR
T1 - Tumor mRNA-transfected dendritic cells stimulate the generation of CTL that recognize neuroblastoma-associated antigens and kill tumor cells
T2 - Immunotherapeutic implications
AU - Morandi, Fabio
AU - Chiesa, Sabrina
AU - Bocca, Paola
AU - Millo, Enrico
AU - Salis, Annalisa
AU - Solari, Massimo
AU - Pistoia, Vito
AU - Prigione, Ignazia
PY - 2006/10
Y1 - 2006/10
N2 - Several observations suggest a potential role of T-cell-mediated immunity in the control of neuroblastoma (NB). However, the generation of NB-specific cytotoxic T lymphocytes (CTL) on T-cell priming with tumor mRNA-transfected dendritic cells (DC) has never been investigated before. In the present study, the feasibility of this strategy has been analyzed, both in healthy donors and in NB patients. Monocyte-derived DC were raised from three human leukocyte antigen (HLA) A2
+ NB patients and seven HLA-A1
+ or HLA-A2
+ healthy donors transfected with mRNA from four NB cell lines and cocultured with autologous CD8
+ lymphocytes. Expanded CTL expressed an effector/memory phenotype and a T cytotoxic 1-like profile of cytokine secretion. CTL specificity was demonstrated by interferon-α release on incubation with HLA-matched NB cell lines. The latter cell lines, but not autologous T-cell blasts, were lysed by CTL in an HLA-restricted manner. Cytotoxicity was found to involve the release of granzyme B. When tested for reactivity against NB-associated antigens, CTL from normal individuals recognized anaplastic lymphoma-associated kinase (ALK) and preferentially expressed antigen of melanoma (PRAME) peptides only, whereas patients' CTL reacted also to survivin, telomerase, and tyrosine hydroxylase peptides. This study demonstrates that DC transfected with NB mRNA induce the generation of patients' CTL specific for different NB-associated antigens, supporting the feasibility of NB T-cell immunotherapy.
AB - Several observations suggest a potential role of T-cell-mediated immunity in the control of neuroblastoma (NB). However, the generation of NB-specific cytotoxic T lymphocytes (CTL) on T-cell priming with tumor mRNA-transfected dendritic cells (DC) has never been investigated before. In the present study, the feasibility of this strategy has been analyzed, both in healthy donors and in NB patients. Monocyte-derived DC were raised from three human leukocyte antigen (HLA) A2
+ NB patients and seven HLA-A1
+ or HLA-A2
+ healthy donors transfected with mRNA from four NB cell lines and cocultured with autologous CD8
+ lymphocytes. Expanded CTL expressed an effector/memory phenotype and a T cytotoxic 1-like profile of cytokine secretion. CTL specificity was demonstrated by interferon-α release on incubation with HLA-matched NB cell lines. The latter cell lines, but not autologous T-cell blasts, were lysed by CTL in an HLA-restricted manner. Cytotoxicity was found to involve the release of granzyme B. When tested for reactivity against NB-associated antigens, CTL from normal individuals recognized anaplastic lymphoma-associated kinase (ALK) and preferentially expressed antigen of melanoma (PRAME) peptides only, whereas patients' CTL reacted also to survivin, telomerase, and tyrosine hydroxylase peptides. This study demonstrates that DC transfected with NB mRNA induce the generation of patients' CTL specific for different NB-associated antigens, supporting the feasibility of NB T-cell immunotherapy.
KW - CTL
KW - Dendritic cells
KW - Human neuroblastoma
KW - Immunotherapy
KW - Tumor-associated antigens
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U2 - 10.1593/neo.06415
DO - 10.1593/neo.06415
M3 - Article
C2 - 17032500
AN - SCOPUS:33749843270
VL - 8
SP - 833
EP - 842
JO - Neoplasia
JF - Neoplasia
SN - 1522-8002
IS - 10
ER -