PMID- 28676668
OWN - NLM
STAT- MEDLINE
DCOM- 20190102
LR  - 20210503
IS  - 1476-5551 (Electronic)
IS  - 0887-6924 (Linking)
VI  - 32
IP  - 2
DP  - 2018 Feb
TI  - The calreticulin (CALR) exon 9 mutations are promising targets for cancer immune 
      therapy.
PG  - 429-437
LID - 10.1038/leu.2017.214 [doi]
AB  - The calreticulin (CALR) exon 9 mutations are found in  approximately 30% of patients with 
      essential thrombocythemia and primary myelofibrosis. Recently, we reported 
      spontaneous immune responses against the CALR mutations. Here, we describe that 
      CALR-mutant (CALRmut)-specific T cells are able to specifically recognize CALRmut 
      cells. First, we established a T-cell culture specific for a CALRmut epitope. 
      These specific T cells were able to recognize several epitopes in the CALRmut C 
      terminus. Next, we established a CALRmut-specific CD4(+) T-cell clone by limiting 
      dilution. These CD4(+) T cells recognized autologous CALRmut monocytes and 
      hematopoietic stem cells, and T-cell recognition of target cells was dependent on 
      the presence of CALR. Furthermore, we showed that the CALRmut response was human 
      leukocyte antigen (HLA)-DR restricted. Finally, we demonstrated that the 
      CALRmut-specific CD4(+) T cells, despite their phenotype, were cytotoxic to 
      autologous CALRmut cells, and that the cytotoxicity was mediated by degranulation 
      of the T cells. In conclusion, the CALR exon 9 mutations are targets for specific 
      T cells and thus are promising targets for cancer immune therapy such as peptide 
      vaccination in patients harboring CALR exon 9 mutations.
FAU - Holmstrom, M O
AU  - Holmstrom MO
AD  - Department of Hematology, Zealand University Hospital, Roskilde, Denmark.
AD  - Center for Cancer Immune Therapy, Department of Hematology, Copenhagen University 
      Hospital at Herlev, Herlev, Denmark.
FAU - Martinenaite, E
AU  - Martinenaite E
AD  - Center for Cancer Immune Therapy, Department of Hematology, Copenhagen University 
      Hospital at Herlev, Herlev, Denmark.
FAU - Ahmad, S M
AU  - Ahmad SM
AD  - Center for Cancer Immune Therapy, Department of Hematology, Copenhagen University 
      Hospital at Herlev, Herlev, Denmark.
FAU - Met, O
AU  - Met O
AD  - Center for Cancer Immune Therapy, Department of Hematology, Copenhagen University 
      Hospital at Herlev, Herlev, Denmark.
AD  - Department of Oncology, Copenhagen University Hospital at Herlev, Herlev, 
      Denmark.
FAU - Friese, C
AU  - Friese C
AD  - Center for Cancer Immune Therapy, Department of Hematology, Copenhagen University 
      Hospital at Herlev, Herlev, Denmark.
FAU - Kjaer, L
AU  - Kjaer L
AD  - Department of Hematology, Zealand University Hospital, Roskilde, Denmark.
FAU - Riley, C H
AU  - Riley CH
AD  - Department of Hematology, Rigshospitalet, Copenhagen, Denmark.
FAU - Thor Straten, P
AU  - Thor Straten P
AUID- ORCID: 0000-0002-4731-4969
AD  - Center for Cancer Immune Therapy, Department of Hematology, Copenhagen University 
      Hospital at Herlev, Herlev, Denmark.
AD  - Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, 
      Denmark.
FAU - Svane, I M
AU  - Svane IM
AD  - Center for Cancer Immune Therapy, Department of Hematology, Copenhagen University 
      Hospital at Herlev, Herlev, Denmark.
AD  - Department of Oncology, Copenhagen University Hospital at Herlev, Herlev, 
      Denmark.
FAU - Hasselbalch, H C
AU  - Hasselbalch HC
AD  - Department of Hematology, Zealand University Hospital, Roskilde, Denmark.
FAU - Andersen, M H
AU  - Andersen MH
AD  - Center for Cancer Immune Therapy, Department of Hematology, Copenhagen University 
      Hospital at Herlev, Herlev, Denmark.
AD  - Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, 
      Denmark.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20170705
PL  - England
TA  - Leukemia
JT  - Leukemia
JID - 8704895
RN  - 0 (CALR protein, human)
RN  - 0 (Calreticulin)
RN  - 0 (HLA Antigens)
RN  - 0 (Vaccines, Subunit)
SB  - IM
MH  - Aged
MH  - CD4-Positive T-Lymphocytes/drug effects/immunology
MH  - Calreticulin/*genetics
MH  - Cytotoxicity, Immunologic/drug effects
MH  - Exons/*drug effects/genetics
MH  - HLA Antigens/drug effects/genetics/immunology
MH  - Humans
MH  - Male
MH  - Mutation/*drug effects/genetics
MH  - Neoplasms/*genetics/immunology/*therapy
MH  - Phenotype
MH  - Primary Myelofibrosis/genetics/immunology
MH  - Thrombocythemia, Essential/genetics/immunology
MH  - Vaccines, Subunit/immunology/*therapeutic use
EDAT- 2017/07/06 06:00
MHDA- 2019/01/03 06:00
CRDT- 2017/07/06 06:00
PHST- 2017/03/22 00:00 [received]
PHST- 2017/06/15 00:00 [revised]
PHST- 2017/06/23 00:00 [accepted]
PHST- 2017/07/06 06:00 [pubmed]
PHST- 2019/01/03 06:00 [medline]
PHST- 2017/07/06 06:00 [entrez]
AID - leu2017214 [pii]
AID - 10.1038/leu.2017.214 [doi]
PST - ppublish
SO  - Leukemia. 2018 Feb;32(2):429-437. doi: 10.1038/leu.2017.214. Epub 2017 Jul 5.