PMID- 23079962
OWN - NLM
STAT- MEDLINE
DCOM- 20130430
LR  - 20211021
IS  - 1476-5551 (Electronic)
IS  - 0887-6924 (Print)
IS  - 0887-6924 (Linking)
VI  - 27
IP  - 3
DP  - 2013 Mar
TI  - Towards effective and safe immunotherapy after allogeneic stem cell 
      transplantation: identification of hematopoietic-specific minor 
      histocompatibility antigen UTA2-1.
PG  - 642-9
LID - 10.1038/leu.2012.277 [doi]
AB  - Donor T cells directed at hematopoietic system-specific minor histocompatibility 
      antigens (mHags) are considered important cellular tools to induce therapeutic 
      graft-versus-tumor (GvT) effects with low risk of graft-versus-host disease after 
      allogeneic stem cell transplantation. To enable the clinical evaluation of the 
      concept of mHag-based immunotherapy and subsequent broad implementation, the 
      identification of more hematopoietic mHags with broad applicability is 
      imperative. Here we describe novel mHag UTA2-1 with ideal characteristics for 
      this purpose. We identified this antigen using genome-wide zygosity-genotype 
      correlation analysis of a mHag-specific CD8(+) cytotoxic T lymphocyte (CTL) clone 
      derived from a multiple myeloma patient who achieved a long-lasting complete 
      remission after donor lymphocyte infusion from an human leukocyte antigen 
      (HLA)-matched sibling. UTA2-1 is a polymorphic peptide presented by the common 
      HLA molecule HLA-A*02:01, which is encoded by the bi-allelic 
      hematopoietic-specific gene C12orf35. Tetramer analyses demonstrated an expansion 
      of UTA2-1-directed T cells in patient blood samples after several donor T-cell 
      infusions that mediated clinical GvT responses. More importantly, UTA2-1-specific 
      CTL effectively lysed mHag(+) hematopoietic cells, including patient myeloma 
      cells, without affecting non-hematopoietic cells. Thus, with the capacity to 
      induce relevant immunotherapeutic CTLs, it's HLA-A*02 restriction and equally 
      balanced phenotype frequency, UTA2-1 is a highly valuable mHag to facilitate 
      clinical application of mHag-based immunotherapy.
FAU - Oostvogels, R
AU  - Oostvogels R
AD  - Department of Clinical Chemistry and Hematology, University Medical Center 
      Utrecht, Utrecht, The Netherlands.
FAU - Minnema, M C
AU  - Minnema MC
FAU - van Elk, M
AU  - van Elk M
FAU - Spaapen, R M
AU  - Spaapen RM
FAU - te Raa, G D
AU  - te Raa GD
FAU - Giovannone, B
AU  - Giovannone B
FAU - Buijs, A
AU  - Buijs A
FAU - van Baarle, D
AU  - van Baarle D
FAU - Kater, A P
AU  - Kater AP
FAU - Griffioen, M
AU  - Griffioen M
FAU - Spierings, E
AU  - Spierings E
FAU - Lokhorst, H M
AU  - Lokhorst HM
FAU - Mutis, T
AU  - Mutis T
LA  - eng
PT  - Case Reports
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20121001
PL  - England
TA  - Leukemia
JT  - Leukemia
JID - 8704895
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (HLA Antigens)
RN  - 0 (Minor Histocompatibility Antigens)
RN  - 0 (RNA, Messenger)
SB  - IM
MH  - Apoptosis
MH  - Biomarkers, Tumor/genetics/metabolism
MH  - Blotting, Western
MH  - Cell Proliferation
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Flow Cytometry
MH  - Gene Expression Profiling
MH  - Graft vs Host Disease/genetics/*immunology/therapy
MH  - Graft vs Leukemia Effect/*immunology
MH  - HLA Antigens/immunology/metabolism
MH  - *Hematopoietic Stem Cell Transplantation
MH  - Humans
MH  - Immunoenzyme Techniques
MH  - *Immunotherapy
MH  - Male
MH  - Middle Aged
MH  - Minor Histocompatibility Antigens/genetics/*immunology/metabolism
MH  - Multiple Myeloma/genetics/*immunology/therapy
MH  - Oligonucleotide Array Sequence Analysis
MH  - RNA, Messenger/genetics
MH  - Real-Time Polymerase Chain Reaction
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - T-Lymphocytes, Cytotoxic/*immunology
MH  - Transplantation, Homologous
PMC - PMC3593180
EDAT- 2012/10/20 06:00
MHDA- 2013/05/01 06:00
CRDT- 2012/10/20 06:00
PHST- 2012/10/20 06:00 [entrez]
PHST- 2012/10/20 06:00 [pubmed]
PHST- 2013/05/01 06:00 [medline]
AID - leu2012277 [pii]
AID - 10.1038/leu.2012.277 [doi]
PST - ppublish
SO  - Leukemia. 2013 Mar;27(3):642-9. doi: 10.1038/leu.2012.277. Epub 2012 Oct 1.