PMID- 21660045
OWN - NLM
STAT- MEDLINE
DCOM- 20111121
LR  - 20211020
IS  - 1476-5551 (Electronic)
IS  - 0887-6924 (Print)
IS  - 0887-6924 (Linking)
VI  - 25
IP  - 10
DP  - 2011 Oct
TI  - Identification of novel myeloma-specific XBP1 peptides able to generate cytotoxic 
      T lymphocytes: a potential therapeutic application in multiple myeloma.
PG  - 1610-9
LID - 10.1038/leu.2011.120 [doi]
AB  - The purpose of these studies was to identify human leukocyte antigen (HLA)-A2(+) 
      immunogenic peptides derived from XBP1 antigens to induce a multiple myeloma 
      (MM)-specific immune response. Six native peptides from non-spliced XBP1 antigen 
      and three native peptides from spliced XBP1 antigen were selected and evaluated 
      for their HLA-A2 specificity. Among them, XBP1(184-192), XBP1 SP(196-204) and 
      XBP1 SP(367-375) peptides showed the highest level of binding affinity, but not 
      stability to HLA-A2 molecules. Novel heteroclitic XBP1 peptides, YISPWILAV or 
      YLFPQLISV, demonstrated a significant improvement in HLA-A2 stability from their 
      native XBP1(184-192) or XBP1 SP(367-375) peptide, respectively. Cytotoxic T 
      lymphocytes generated by repeated stimulation of CD3(+) T cells with each 
      HLA-A2-specific heteroclitic peptide showed an increased percentage of CD8(+) 
      (cytotoxic) and CD69(+)/CD45RO(+) (activated memory) T cells and a lower 
      percentage of CD4(+) (helper) and CD45RA(+)/CCR7(+) (naive) T cells, which were 
      distinct from the control T cells. Functionally, the cytotoxic T lymphocytes 
      (CTL) demonstrated MM-specific and HLA-A2-restricted proliferation, interferon-gamma 
      secretion and cytotoxic activity in response to MM cell lines and importantly, 
      cytotoxicity against primary MM cells. These data demonstrate the distinct 
      immunogenic characteristics of unique heteroclitic XBP1 peptides, which induce 
      MM-specific CTLs and highlights their potential application for immunotherapy to 
      treat the patients with MM or its pre-malignant condition.
FAU - Bae, J
AU  - Bae J
AD  - Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, 
      USA.
FAU - Carrasco, R
AU  - Carrasco R
FAU - Lee, A-H
AU  - Lee AH
FAU - Prabhala, R
AU  - Prabhala R
FAU - Tai, Y-T
AU  - Tai YT
FAU - Anderson, K C
AU  - Anderson KC
FAU - Munshi, N C
AU  - Munshi NC
LA  - eng
GR  - P50-100707/PHS HHS/United States
GR  - R01-50947/PHS HHS/United States
GR  - P01-78378/PHS HHS/United States
GR  - P01 CA078378/CA/NCI NIH HHS/United States
GR  - P01 CA155258/CA/NCI NIH HHS/United States
GR  - R01 CA050947/CA/NCI NIH HHS/United States
GR  - P50 CA100707/CA/NCI NIH HHS/United States
GR  - P01-155258/PHS HHS/United States
GR  - R01-129295/PHS HHS/United States
GR  - R01 CA124929/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20110610
PL  - England
TA  - Leukemia
JT  - Leukemia
JID - 8704895
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Peptide Fragments)
RN  - 0 (Regulatory Factor X Transcription Factors)
RN  - 0 (Transcription Factors)
RN  - 0 (X-Box Binding Protein 1)
RN  - 0 (XBP1 protein, human)
SB  - IM
MH  - Amino Acid Sequence
MH  - Cell Line, Tumor
MH  - Cell Proliferation
MH  - DNA-Binding Proteins/chemistry/*metabolism
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Humans
MH  - Multiple Myeloma/*metabolism/therapy
MH  - Peptide Fragments/immunology/*metabolism/therapeutic use
MH  - Regulatory Factor X Transcription Factors
MH  - T-Lymphocytes, Cytotoxic/cytology/*immunology
MH  - Transcription Factors/chemistry/*metabolism
MH  - X-Box Binding Protein 1
PMC - PMC3483794
MID - NIHMS275832
COIS- CONFLICT OF INTEREST There are no competing financial conflicts of interest in 
      relation to the work described.
EDAT- 2011/06/11 06:00
MHDA- 2011/12/13 00:00
PMCR- 2012/10/30
CRDT- 2011/06/11 06:00
PHST- 2011/06/11 06:00 [entrez]
PHST- 2011/06/11 06:00 [pubmed]
PHST- 2011/12/13 00:00 [medline]
PHST- 2012/10/30 00:00 [pmc-release]
AID - leu2011120 [pii]
AID - 10.1038/leu.2011.120 [doi]
PST - ppublish
SO  - Leukemia. 2011 Oct;25(10):1610-9. doi: 10.1038/leu.2011.120. Epub 2011 Jun 10.