PMID- 20844564
OWN - NLM
STAT- MEDLINE
DCOM- 20101222
LR  - 20201222
IS  - 1476-5551 (Electronic)
IS  - 0887-6924 (Linking)
VI  - 24
IP  - 11
DP  - 2010 Nov
TI  - Targeting B cell leukemia with highly specific allogeneic T cells with a public 
      recognition motif.
PG  - 1901-9
LID - 10.1038/leu.2010.186 [doi]
AB  - The possibility that allogeneic T cells may be targeted to leukemia has important 
      therapeutic implications. As most tumor antigens represent self-proteins, 
      high-avidity tumor-specific T cells are largely deleted from the repertoire of 
      the patient. In contrast, T cells from major histocompatibility complex 
      (MHC)-mismatched donors provide naive repertoires wherein such cells have not 
      been systematically eliminated. Yet, evidence for peptide degeneracy or 
      poly-specificity warrants caution in the use of foreign human leukocyte antigen 
      (HLA) or peptide complexes as therapeutic targets. Here, we cocultured 
      HLA-A(*)0201-negative T cells with autologous dendritic cells engineered to 
      present HLA-A(*)0201 complexed with a peptide from the B cell antigen CD20 
      (CD20p). HLA-A(*)0201/CD20p pentamer-reactive CD8(+) T cells were readily 
      obtained from all donors. The polyclonal cells showed exquisite peptide and MHC 
      specificity, and efficiently killed HLA-A(*)0201-positive B cells, including 
      primary chronic lymphocytic leukemia cells. The T cell receptor (TCR) sequences 
      displayed a novel type of conservation, with extensive homology in the TCR beta 
      chain complementarity-determining region 3 and in J, but not V, region. This is 
      surprising, as the donors were HLA disparate and their TCR repertoires are 
      expected to show little overlap. The results demonstrate the first public 
      recognition motif for an allogeneic HLA/peptide complex. The allo-restricted T 
      cells or TCRs could provide graft-versus-leukemia in the absence of 
      graft-versus-host disease.
FAU - Abrahamsen, I W
AU  - Abrahamsen IW
AD  - Institute of Immunology, Oslo University Hospital Rikshospitalet, Oslo, Norway.
FAU - Stronen, E
AU  - Stronen E
FAU - Walchli, S
AU  - Walchli S
FAU - Johansen, J N
AU  - Johansen JN
FAU - Kjellevoll, S
AU  - Kjellevoll S
FAU - Kumari, S
AU  - Kumari S
FAU - Komada, M
AU  - Komada M
FAU - Gaudernack, G
AU  - Gaudernack G
FAU - Tjonnfjord, G
AU  - Tjonnfjord G
FAU - Toebes, M
AU  - Toebes M
FAU - Schumacher, T N
AU  - Schumacher TN
FAU - Lund-Johansen, F
AU  - Lund-Johansen F
FAU - Olweus, J
AU  - Olweus J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100916
PL  - England
TA  - Leukemia
JT  - Leukemia
JID - 8704895
RN  - 0 (Antigens, CD20)
RN  - 0 (Autoantigens)
RN  - 0 (HLA Antigens)
RN  - 0 (HLA-A Antigens)
RN  - 0 (HLA-A*02:01 antigen)
RN  - 0 (HLA-A2 Antigen)
RN  - 0 (Isoantigens)
RN  - 0 (Receptors, Antigen, T-Cell, alpha-beta)
SB  - IM
MH  - Antibody Specificity
MH  - Antigens, CD20/immunology
MH  - Autoantigens/immunology
MH  - B-Lymphocytes/immunology
MH  - Dendritic Cells/immunology
MH  - Flow Cytometry
MH  - HEK293 Cells/immunology
MH  - HLA Antigens/immunology
MH  - HLA-A Antigens/immunology
MH  - HLA-A2 Antigen
MH  - Humans
MH  - Isoantigens/*immunology
MH  - Leukemia, B-Cell/*immunology
MH  - Receptors, Antigen, T-Cell, alpha-beta/immunology
MH  - T-Lymphocytes/*immunology
EDAT- 2010/09/17 06:00
MHDA- 2010/12/24 06:00
CRDT- 2010/09/17 06:00
PHST- 2010/09/17 06:00 [entrez]
PHST- 2010/09/17 06:00 [pubmed]
PHST- 2010/12/24 06:00 [medline]
AID - leu2010186 [pii]
AID - 10.1038/leu.2010.186 [doi]
PST - ppublish
SO  - Leukemia. 2010 Nov;24(11):1901-9. doi: 10.1038/leu.2010.186. Epub 2010 Sep 16.