PMID- 27689397
OWN - NLM
STAT- MEDLINE
DCOM- 20180213
LR  - 20181113
IS  - 1949-2553 (Electronic)
IS  - 1949-2553 (Linking)
VI  - 7
IP  - 44
DP  - 2016 Nov 1
TI  - A CD22-reactive TCR from the T-cell allorepertoire for the treatment of acute 
      lymphoblastic leukemia by TCR gene transfer.
PG  - 71536-71547
LID - 10.18632/oncotarget.12247 [doi]
AB  - CD22 is currently evaluated as a target-antigen for the treatment of B-cell 
      malignancies using chimeric antigen receptor (CAR)-engineered T-cells or 
      monoclonal antibodies (mAbs). CAR- and mAbs-based immunotherapies have been 
      successfully applied targeting other antigens, however, occurrence of refractory 
      disease to these interventions urges the identification of additional strategies. 
      Here, we identified a TCR recognizing the CD22-derived peptide RPFPPHIQL 
      (CD22RPF) presented in human leukocyte antigen (HLA)-B*07:02. To overcome 
      tolerance to self-antigens such as CD22, we exploited the immunogenicity of 
      allogeneic HLA. CD22RPF-specific T-cell clone 9D4 was isolated from a healthy 
      HLA-B*07:02neg individual, efficiently produced cytokines upon stimulation with 
      primary acute lymphoblastic leukemia and healthy B-cells, but did not react 
      towards healthy hematopoietic and nonhematopoietic cell subsets, including 
      dendritic cells (DCs) and macrophages expressing low levels of CD22. Gene 
      transfer of TCR-9D4 installed potent CD22-specificity onto recipient CD8+ T-cells 
      that recognized and lysed primary B-cell leukemia. TCR-transduced T-cells spared 
      healthy CD22neg hematopoietic cell subsets but weakly lysed CD22low-expressing 
      DCs and macrophages. CD22-specific TCR-engineered T-cells could form an 
      additional immunotherapeutic strategy with a complementary role to CAR- and 
      antibody-based interventions in the treatment of B-cell malignancies. However, 
      CD22 expression on non-B-cells may limit the attractiveness of CD22 as 
      target-antigen in cellular immunotherapy.
FAU - Jahn, Lorenz
AU  - Jahn L
AD  - Department of Hematology, Leiden University Medical Center, 2300 RC Leiden, The 
      Netherlands.
FAU - Hagedoorn, Renate S
AU  - Hagedoorn RS
AD  - Department of Hematology, Leiden University Medical Center, 2300 RC Leiden, The 
      Netherlands.
FAU - van der Steen, Dirk M
AU  - van der Steen DM
AD  - Department of Hematology, Leiden University Medical Center, 2300 RC Leiden, The 
      Netherlands.
FAU - Hombrink, Pleun
AU  - Hombrink P
AD  - Department of Hematology, Leiden University Medical Center, 2300 RC Leiden, The 
      Netherlands.
AD  - Department of Hematopoiesis, Sanquin Research, 1006 AD Amsterdam, The 
      Netherlands.
FAU - Kester, Michel G D
AU  - Kester MG
AD  - Department of Hematology, Leiden University Medical Center, 2300 RC Leiden, The 
      Netherlands.
FAU - Schoonakker, Marjolein P
AU  - Schoonakker MP
AD  - Department of Hematology, Leiden University Medical Center, 2300 RC Leiden, The 
      Netherlands.
FAU - de Ridder, Danielle
AU  - de Ridder D
AD  - Department of Hematology, Leiden University Medical Center, 2300 RC Leiden, The 
      Netherlands.
FAU - van Veelen, Peter A
AU  - van Veelen PA
AD  - Center for Proteomics and Metabolomics, Leiden University Medical Center, 2300 RC 
      Leiden, The Netherlands.
FAU - Falkenburg, J H Frederik
AU  - Falkenburg JH
AD  - Department of Hematology, Leiden University Medical Center, 2300 RC Leiden, The 
      Netherlands.
FAU - Heemskerk, Mirjam H M
AU  - Heemskerk MH
AD  - Department of Hematology, Leiden University Medical Center, 2300 RC Leiden, The 
      Netherlands.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Oncotarget
JT  - Oncotarget
JID - 101532965
RN  - 0 (CD22 protein, human)
RN  - 0 (Epitopes)
RN  - 0 (HLA-B Antigens)
RN  - 0 (Receptors, Antigen, T-Cell)
RN  - 0 (Sialic Acid Binding Ig-like Lectin 2)
SB  - IM
MH  - CD8-Positive T-Lymphocytes/*immunology
MH  - Epitopes
MH  - Gene Transfer Techniques
MH  - HLA-B Antigens/immunology
MH  - Humans
MH  - Immunotherapy, Adoptive
MH  - Precursor Cell Lymphoblastic Leukemia-Lymphoma/*therapy
MH  - Receptors, Antigen, T-Cell/*genetics
MH  - Sialic Acid Binding Ig-like Lectin 2/*immunology
PMC - PMC5342099
OTO - NOTNLM
OT  - CD22
OT  - TCR gene transfer
OT  - acute lymphoblastic leukemia
OT  - allogeneic HLA
OT  - immunotherapy
COIS- CONFLICTS OF INTEREST The authors declare no competing interests.
EDAT- 2016/10/01 06:00
MHDA- 2018/02/14 06:00
PMCR- 2016/11/01
CRDT- 2016/10/01 06:00
PHST- 2016/06/13 00:00 [received]
PHST- 2016/09/19 00:00 [accepted]
PHST- 2016/10/01 06:00 [pubmed]
PHST- 2018/02/14 06:00 [medline]
PHST- 2016/10/01 06:00 [entrez]
PHST- 2016/11/01 00:00 [pmc-release]
AID - 12247 [pii]
AID - 10.18632/oncotarget.12247 [doi]
PST - ppublish
SO  - Oncotarget. 2016 Nov 1;7(44):71536-71547. doi: 10.18632/oncotarget.12247.