PMID- 17032500
OWN - NLM
STAT- MEDLINE
DCOM- 20061201
LR  - 20210105
IS  - 1476-5586 (Electronic)
IS  - 1522-8002 (Print)
IS  - 1476-5586 (Linking)
VI  - 8
IP  - 10
DP  - 2006 Oct
TI  - Tumor mRNA-transfected dendritic cells stimulate the generation of CTL that 
      recognize neuroblastoma-associated antigens and kill tumor cells: 
      immunotherapeutic implications.
PG  - 833-42
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-gamma 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.
FAU - Morandi, Fabio
AU  - Morandi F
AD  - Laboratory of Oncology, G. Gaslini Children's Hospital, Genoa, Italy. 
      fabiomorandi@ospedale-gaslini.ge.it
FAU - Chiesa, Sabrina
AU  - Chiesa S
FAU - Bocca, Paola
AU  - Bocca P
FAU - Millo, Enrico
AU  - Millo E
FAU - Salis, Annalisa
AU  - Salis A
FAU - Solari, Massimo
AU  - Solari M
FAU - Pistoia, Vito
AU  - Pistoia V
FAU - Prigione, Ignazia
AU  - Prigione I
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Neoplasia
JT  - Neoplasia (New York, N.Y.)
JID - 100886622
RN  - 0 (Antigens, Neoplasm)
RN  - 0 (HLA-A2 Antigen)
RN  - 0 (RNA, Messenger)
RN  - EC 2.7.10.1 (ALK protein, human)
RN  - EC 2.7.10.1 (Anaplastic Lymphoma Kinase)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
SB  - IM
MH  - Anaplastic Lymphoma Kinase
MH  - Antigens, Neoplasm/immunology
MH  - Dendritic Cells/*physiology
MH  - HLA-A2 Antigen
MH  - Humans
MH  - Immunotherapy/*methods
MH  - Neuroblastoma/*immunology/*therapy
MH  - Protein-Tyrosine Kinases/immunology
MH  - RNA, Messenger
MH  - Receptor Protein-Tyrosine Kinases
MH  - T-Lymphocytes, Cytotoxic/*immunology
MH  - Transfection
MH  - Tumor Cells, Cultured
PMC - PMC1715922
EDAT- 2006/10/13 09:00
MHDA- 2006/12/09 09:00
PMCR- 2006/10/01
CRDT- 2006/10/13 09:00
PHST- 2006/10/13 09:00 [pubmed]
PHST- 2006/12/09 09:00 [medline]
PHST- 2006/10/13 09:00 [entrez]
PHST- 2006/10/01 00:00 [pmc-release]
AID - 06415 [pii]
AID - 10.1593/neo.06415 [doi]
PST - ppublish
SO  - Neoplasia. 2006 Oct;8(10):833-42. doi: 10.1593/neo.06415.