PMID- 16778141
OWN - NLM
STAT- MEDLINE
DCOM- 20061102
LR  - 20210206
IS  - 0006-4971 (Print)
IS  - 1528-0020 (Electronic)
IS  - 0006-4971 (Linking)
VI  - 108
IP  - 8
DP  - 2006 Oct 15
TI  - Identification of an immunogenic CD8+ T-cell epitope derived from gamma-globin, a 
      putative tumor-associated antigen for juvenile myelomonocytic leukemia.
PG  - 2662-8
AB  - Juvenile myelomonocytic leukemia (JMML) is a rare clonal myeloproliferative 
      disorder. Although allogeneic stem cell transplantation can induce long-term 
      remissions, relapse rates remain high and innovative approaches are needed. Since 
      donor lymphocyte infusions have clinical activity in JMML, T-cell-mediated 
      immunotherapy could provide a nonredundant treatment approach to compliment 
      current therapies. Gamma-globin, an oncofetal protein overexpressed by clonogenic 
      JMML cells, may serve as a target of an antitumor immune response. We predicted 5 
      gamma-globin-derived peptides as potential human leukocyte antigen (HLA)-A2 
      restricted cytotoxic T lymphocyte (CTL) epitopes and showed that 4 (g031, g071, 
      g105, and g106) bind A2 molecules in vitro. Using an artificial 
      antigen-presenting cell (aAPC) that can process both the N- and C-termini of 
      endogenously expressed proteins, we biochemically confirmed that g105 is 
      naturally processed and presented by cell surface A2. Furthermore, g105-specific 
      CD8(+) CTLs generated from A2-positive healthy donors were able to specifically 
      cytolyze gamma-globin(+), but not gamma-globin(-) JMML cells in an A2-restricted 
      manner. These results suggest that this aAPC-based approach enables the 
      biochemical identification of CD8(+) T-cell epitopes that are processed and 
      presented by intact cells, and that CTL immunotherapy of JMML could be directed 
      against the gamma-globin-derived epitope g105.
FAU - Hirano, Naoto
AU  - Hirano N
AD  - Department of Medical Oncology, Dana-Farber Cancer Institute, 44 Binney St, 
      Boston, MA 02115, USA. naoto_hirano@dfci.harvard.edu
FAU - Butler, Marcus O
AU  - Butler MO
FAU - Xia, Zhinan
AU  - Xia Z
FAU - Berezovskaya, Alla
AU  - Berezovskaya A
FAU - Murray, Andrew P
AU  - Murray AP
FAU - Ansen, Sascha
AU  - Ansen S
FAU - Kojima, Seiji
AU  - Kojima S
FAU - Nadler, Lee M
AU  - Nadler LM
LA  - eng
GR  - CA 87720/CA/NCI NIH HHS/United States
GR  - CA 92625-04/CA/NCI NIH HHS/United States
GR  - HL 54785-08/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20060615
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Antigens, Neoplasm)
RN  - 0 (Epitopes)
RN  - 0 (HLA-A2 Antigen)
RN  - 9004-22-2 (Globins)
SB  - IM
MH  - Antigen-Presenting Cells/immunology
MH  - Antigens, Neoplasm/genetics/*isolation & purification
MH  - CD8-Positive T-Lymphocytes/*immunology
MH  - Child
MH  - Epitopes/isolation & purification
MH  - Globins/*immunology
MH  - HLA-A2 Antigen/metabolism
MH  - Humans
MH  - In Vitro Techniques
MH  - Leukemia, Myelomonocytic, Acute/genetics/*immunology
PMC - PMC1895581
EDAT- 2006/06/17 09:00
MHDA- 2006/11/03 09:00
PMCR- 2007/10/15
CRDT- 2006/06/17 09:00
PHST- 2006/06/17 09:00 [pubmed]
PHST- 2006/11/03 09:00 [medline]
PHST- 2006/06/17 09:00 [entrez]
PHST- 2007/10/15 00:00 [pmc-release]
AID - S0006-4971(20)52451-8 [pii]
AID - 2662 [pii]
AID - 10.1182/blood-2006-04-017566 [doi]
PST - ppublish
SO  - Blood. 2006 Oct 15;108(8):2662-8. doi: 10.1182/blood-2006-04-017566. Epub 2006 
      Jun 15.