PMID- 20400962
OWN - NLM
STAT- MEDLINE
DCOM- 20100702
LR  - 20211020
IS  - 1546-170X (Electronic)
IS  - 1078-8956 (Linking)
VI  - 16
IP  - 5
DP  - 2010 May
TI  - Lethal graft-versus-host disease in mouse models of T cell receptor gene therapy.
PG  - 565-70, 1p following 570
LID - 10.1038/nm.2128 [doi]
AB  - The transfer of T cell receptor (TCR) genes can be used to induce immune 
      reactivity toward defined antigens to which endogenous T cells are insufficiently 
      reactive. This approach, which is called TCR gene therapy, is being developed to 
      target tumors and pathogens, and its clinical testing has commenced in patients 
      with cancer. In this study we show that lethal cytokine-driven autoimmune 
      pathology can occur in mouse models of TCR gene therapy under conditions that 
      closely mimic the clinical setting. We show that the pairing of introduced and 
      endogenous TCR chains in TCR gene-modified T cells leads to the formation of 
      self-reactive TCRs that are responsible for the observed autoimmunity. 
      Furthermore, we demonstrate that adjustments in the design of gene therapy 
      vectors and target T cell populations can be used to reduce the risk of TCR gene 
      therapy-induced autoimmune pathology.
FAU - Bendle, Gavin M
AU  - Bendle GM
AD  - Division of Immunology, The Netherlands Cancer Institute, Amsterdam, The 
      Netherlands. g.bendle@nki.nl
FAU - Linnemann, Carsten
AU  - Linnemann C
FAU - Hooijkaas, Anna I
AU  - Hooijkaas AI
FAU - Bies, Laura
AU  - Bies L
FAU - de Witte, Moniek A
AU  - de Witte MA
FAU - Jorritsma, Annelies
AU  - Jorritsma A
FAU - Kaiser, Andrew D M
AU  - Kaiser AD
FAU - Pouw, Nadine
AU  - Pouw N
FAU - Debets, Reno
AU  - Debets R
FAU - Kieback, Elisa
AU  - Kieback E
FAU - Uckert, Wolfgang
AU  - Uckert W
FAU - Song, Ji-Ying
AU  - Song JY
FAU - Haanen, John B A G
AU  - Haanen JB
FAU - Schumacher, Ton N M
AU  - Schumacher TN
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100418
PL  - United States
TA  - Nat Med
JT  - Nature medicine
JID - 9502015
RN  - 0 (Receptors, Antigen, T-Cell)
SB  - IM
CIN - Nat Med. 2010 May;16(5):520-1. PMID: 20448573
CIN - Immunotherapy. 2010 Nov;2(6):791-4. PMID: 21091111
MH  - Animals
MH  - *Genes, T-Cell Receptor
MH  - Genetic Therapy/*methods
MH  - Graft vs Host Disease/immunology/*pathology
MH  - Humans
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Models, Animal
MH  - Neoplasms/genetics/immunology/*therapy
MH  - Receptors, Antigen, T-Cell/*genetics/immunology
MH  - T-Lymphocytes/metabolism
EDAT- 2010/04/20 06:00
MHDA- 2010/07/03 06:00
CRDT- 2010/04/20 06:00
PHST- 2010/01/08 00:00 [received]
PHST- 2010/02/25 00:00 [accepted]
PHST- 2010/04/20 06:00 [entrez]
PHST- 2010/04/20 06:00 [pubmed]
PHST- 2010/07/03 06:00 [medline]
AID - nm.2128 [pii]
AID - 10.1038/nm.2128 [doi]
PST - ppublish
SO  - Nat Med. 2010 May;16(5):565-70, 1p following 570. doi: 10.1038/nm.2128. Epub 2010 
      Apr 18.