PMID- 26389576
OWN - NLM
STAT- MEDLINE
DCOM- 20160329
LR  - 20210105
IS  - 1546-1696 (Electronic)
IS  - 1087-0156 (Print)
IS  - 1087-0156 (Linking)
VI  - 33
IP  - 10
DP  - 2015 Oct
TI  - Therapeutic bispecific T-cell engager antibody targeting the intracellular 
      oncoprotein WT1.
PG  - 1079-86
LID - 10.1038/nbt.3349 [doi]
AB  - Intracellular tumor antigens presented on the cell surface in the context of 
      human leukocyte antigen (HLA) molecules have been targeted by T cell-based 
      therapies, but there has been little progress in developing small-molecule drugs 
      or antibodies directed to these antigens. Here we describe a bispecific T-cell 
      engager (BiTE) antibody derived from a T-cell receptor (TCR)-mimic monoclonal 
      antibody (mAb) ESK1, which binds a peptide derived from the intracellular 
      oncoprotein WT1 presented on HLA-A*02:01. Despite the very low density of the 
      complexes at the cell surface, ESK1-BiTE selectively activated and induced 
      proliferation of cytolytic human T cells that killed cells from multiple 
      leukemias and solid tumors in vitro and in mice. We also discovered that in an 
      autologous in vitro setting, ESK1-BiTE induced a robust secondary CD8 T-cell 
      response specific for tumor-associated antigens other than WT1. Our study 
      provides an approach that targets tumor-specific intracellular antigens without 
      using cell therapy and suggests that epitope spreading could contribute to the 
      therapeutic efficacy of this BiTE.
FAU - Dao, Tao
AU  - Dao T
AD  - Memorial Sloan Kettering Cancer Center, New York, New York, USA.
FAU - Pankov, Dmitry
AU  - Pankov D
AD  - Memorial Sloan Kettering Cancer Center, New York, New York, USA.
FAU - Scott, Andrew
AU  - Scott A
AD  - Memorial Sloan Kettering Cancer Center, New York, New York, USA.
AD  - Weill Cornell Medical College, New York, New York, USA.
FAU - Korontsvit, Tatyana
AU  - Korontsvit T
AD  - Memorial Sloan Kettering Cancer Center, New York, New York, USA.
FAU - Zakhaleva, Victoriya
AU  - Zakhaleva V
AD  - Memorial Sloan Kettering Cancer Center, New York, New York, USA.
FAU - Xu, Yiyang
AU  - Xu Y
AD  - Eureka Therapeutics, Emeryville, California, USA.
FAU - Xiang, Jingyi
AU  - Xiang J
AD  - Eureka Therapeutics, Emeryville, California, USA.
FAU - Yan, Su
AU  - Yan S
AD  - Eureka Therapeutics, Emeryville, California, USA.
FAU - de Morais Guerreiro, Manuel Direito
AU  - de Morais Guerreiro MD
AD  - Memorial Sloan Kettering Cancer Center, New York, New York, USA.
FAU - Veomett, Nicholas
AU  - Veomett N
AD  - Memorial Sloan Kettering Cancer Center, New York, New York, USA.
AD  - Weill Cornell Medical College, New York, New York, USA.
FAU - Dubrovsky, Leonid
AU  - Dubrovsky L
AD  - Memorial Sloan Kettering Cancer Center, New York, New York, USA.
FAU - Curcio, Michael
AU  - Curcio M
AD  - Memorial Sloan Kettering Cancer Center, New York, New York, USA.
FAU - Doubrovina, Ekaterina
AU  - Doubrovina E
AD  - Memorial Sloan Kettering Cancer Center, New York, New York, USA.
FAU - Ponomarev, Vladimir
AU  - Ponomarev V
AD  - Memorial Sloan Kettering Cancer Center, New York, New York, USA.
FAU - Liu, Cheng
AU  - Liu C
AD  - Eureka Therapeutics, Emeryville, California, USA.
FAU - O'Reilly, Richard J
AU  - O'Reilly RJ
AD  - Memorial Sloan Kettering Cancer Center, New York, New York, USA.
AD  - Weill Cornell Medical College, New York, New York, USA.
FAU - Scheinberg, David A
AU  - Scheinberg DA
AD  - Memorial Sloan Kettering Cancer Center, New York, New York, USA.
AD  - Weill Cornell Medical College, New York, New York, USA.
LA  - eng
GR  - R01 CA055349/CA/NCI NIH HHS/United States
GR  - T32 CA062948/CA/NCI NIH HHS/United States
GR  - P01 CA023766/CA/NCI NIH HHS/United States
GR  - P30 CA008748/CA/NCI NIH HHS/United States
GR  - R01 CA 55349/CA/NCI NIH HHS/United States
GR  - P01 CA23766/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20150921
PL  - United States
TA  - Nat Biotechnol
JT  - Nature biotechnology
JID - 9604648
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antigens, Neoplasm)
RN  - 0 (Cancer Vaccines)
RN  - 0 (Oncogene Proteins)
RN  - 0 (Repressor Proteins)
RN  - 0 (WT1 Proteins)
RN  - 0 (WT1 protein, mouse)
SB  - IM
CIN - Nat Biotechnol. 2015 Oct;33(10):1040-1. PMID: 26448086
CIN - Nat Rev Drug Discov. 2015 Nov;14(11):749. PMID: 26514861
MH  - Animals
MH  - Antibodies, Monoclonal/immunology/*therapeutic use
MH  - Antigens, Neoplasm/immunology
MH  - Cancer Vaccines/immunology/therapeutic use
MH  - Cell Line, Tumor
MH  - Humans
MH  - Mice
MH  - Molecular Targeted Therapy/methods
MH  - Neoplasms, Experimental/*immunology/*therapy
MH  - Oncogene Proteins/immunology
MH  - Repressor Proteins/*immunology
MH  - T-Lymphocytes/*immunology
MH  - Treatment Outcome
MH  - WT1 Proteins
PMC - PMC4600043
MID - NIHMS725861
EDAT- 2015/09/22 06:00
MHDA- 2016/03/30 06:00
PMCR- 2016/04/01
CRDT- 2015/09/22 06:00
PHST- 2015/02/20 00:00 [received]
PHST- 2015/07/29 00:00 [accepted]
PHST- 2015/09/22 06:00 [entrez]
PHST- 2015/09/22 06:00 [pubmed]
PHST- 2016/03/30 06:00 [medline]
PHST- 2016/04/01 00:00 [pmc-release]
AID - nbt.3349 [pii]
AID - 10.1038/nbt.3349 [doi]
PST - ppublish
SO  - Nat Biotechnol. 2015 Oct;33(10):1079-86. doi: 10.1038/nbt.3349. Epub 2015 Sep 21.