PMID- 23528871
OWN - NLM
STAT- MEDLINE
DCOM- 20130916
LR  - 20220409
IS  - 1476-5551 (Electronic)
IS  - 0887-6924 (Print)
IS  - 0887-6924 (Linking)
VI  - 27
IP  - 7
DP  - 2013 Jul
TI  - Generation of multi-leukemia antigen-specific T cells to enhance the 
      graft-versus-leukemia effect after allogeneic stem cell transplant.
PG  - 1538-47
LID - 10.1038/leu.2013.66 [doi]
AB  - Adoptive immunotherapy with ex vivo expanded T cells is a promising approach to 
      prevent or treat leukemia. Myeloid leukemias express tumor-associated antigens 
      (TAA) that induce antigen-specific cytotoxic T lymphocyte (CTL) responses in 
      healthy individuals. We explored the feasibility of generating TAA-specific CTLs 
      from stem cell donors of patients with myeloid leukemia to enhance the 
      graft-versus-leukemia effect after stem cell transplantation. CTL lines were 
      manufactured from peripheral blood of 10 healthy donors by stimulation with 15mer 
      peptide libraries of five TAA (proteinase 3 (Pr3), preferentially expressed 
      antigen in melanoma, Wilms tumor gene 1 (WT1), human neutrophil elastase (NE) and 
      melanoma-associated antigen A3) known to be expressed in myeloid leukemias. All 
      CTL lines responded to the mix of five TAA and were multi-specific as assessed by 
      interferon-gamma enzyme-linked immunospot. Although donors showed individual patterns 
      of antigen recognition, all responded comparably to the TAAmix. Immunogenic 
      peptides of WT1, Pr3 or NE could be identified by epitope mapping in all donor 
      CTL lines. In vitro experiments showed recognition of partially human leukocyte 
      antigen (HLA)-matched myeloid leukemia blasts. These findings support the 
      development of a single clinical grade multi-tumor antigen-specific T-cell 
      product from the stem cell source, capable of broad reactivity against myeloid 
      malignancies for use in donor-recipient pairs without limitation to a certain 
      HLA-type.
FAU - Weber, G
AU  - Weber G
AD  - Center for Cell and Gene Therapy, Baylor College of Medicine, The Methodist 
      Hospital and Texas Children's Hospital, Houston, TX 77030, USA.
FAU - Gerdemann, U
AU  - Gerdemann U
FAU - Caruana, I
AU  - Caruana I
FAU - Savoldo, B
AU  - Savoldo B
FAU - Hensel, N F
AU  - Hensel NF
FAU - Rabin, K R
AU  - Rabin KR
FAU - Shpall, E J
AU  - Shpall EJ
FAU - Melenhorst, J J
AU  - Melenhorst JJ
FAU - Leen, A M
AU  - Leen AM
FAU - Barrett, A J
AU  - Barrett AJ
FAU - Bollard, C M
AU  - Bollard CM
LA  - eng
GR  - P01 CA148600/CA/NCI NIH HHS/United States
GR  - P30 CA016672/CA/NCI NIH HHS/United States
GR  - R21 CA149967/CA/NCI NIH HHS/United States
GR  - 1P01CA148600-01/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20130301
PL  - England
TA  - Leukemia
JT  - Leukemia
JID - 8704895
RN  - 0 (Antigens, Neoplasm)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Peptide Fragments)
RN  - 0 (WT1 Proteins)
RN  - 0 (thymus-leukemia antigens)
RN  - EC 3.4.21.37 (Leukocyte Elastase)
RN  - EC 3.4.21.76 (Myeloblastin)
SB  - IM
MH  - Antigens, Neoplasm/immunology
MH  - Cell Line
MH  - Dendritic Cells/cytology/immunology
MH  - Epitope Mapping
MH  - Graft vs Leukemia Effect/*immunology
MH  - Hematopoietic Stem Cell Transplantation/*methods
MH  - Histocompatibility Testing
MH  - Humans
MH  - Immunophenotyping
MH  - Leukemia, Myeloid/immunology/*therapy
MH  - Leukocyte Elastase/immunology
MH  - Membrane Glycoproteins/*immunology
MH  - Myeloblastin/immunology
MH  - Peptide Fragments/immunology
MH  - Recurrence
MH  - T-Lymphocytes, Cytotoxic/*cytology/*immunology
MH  - Tissue Donors
MH  - Transplantation, Homologous
MH  - WT1 Proteins/immunology
PMC - PMC3867129
MID - NIHMS499272
COIS- Conflict of Interest: The authors declare no conflict of interest.
EDAT- 2013/03/27 06:00
MHDA- 2013/09/17 06:00
PMCR- 2014/07/01
CRDT- 2013/03/27 06:00
PHST- 2012/12/20 00:00 [received]
PHST- 2013/02/07 00:00 [revised]
PHST- 2013/02/20 00:00 [accepted]
PHST- 2013/03/27 06:00 [entrez]
PHST- 2013/03/27 06:00 [pubmed]
PHST- 2013/09/17 06:00 [medline]
PHST- 2014/07/01 00:00 [pmc-release]
AID - leu201366 [pii]
AID - 10.1038/leu.2013.66 [doi]
PST - ppublish
SO  - Leukemia. 2013 Jul;27(7):1538-47. doi: 10.1038/leu.2013.66. Epub 2013 Mar 1.