PMID- 18323790
OWN - NLM
STAT- MEDLINE
DCOM- 20080916
LR  - 20121115
IS  - 1476-5462 (Electronic)
IS  - 0969-7128 (Linking)
VI  - 15
IP  - 13
DP  - 2008 Jul
TI  - Adenovirus targeting to HLA-A1/MAGE-A1-positive tumor cells by fusing a 
      single-chain T-cell receptor with minor capsid protein IX.
PG  - 978-89
LID - 10.1038/gt.2008.26 [doi]
AB  - Adenovirus vectors have great potential in cancer gene therapy. Targeting of 
      cancer-testis (CT) antigens, which are specifically presented at the surface of 
      tumor cells by human leukocyte antigen (HLA) class I molecules, is an attractive 
      option. In this study, a single-chain T-cell receptor (scTCR) directed against 
      the CT antigen melanoma-associated antigen (MAGE)-A1 in complex with the HLA 
      class I molecule of haplotype HLA-A1 is fused with the C terminus of the 
      adenovirus minor capsid protein IX. Propagation of a protein-IX 
      (pIX)-gene-deleted human adenovirus 5 (HAdV-5) vector on cells that 
      constitutively express the pIXscTCR fusion protein yielded viral particles with 
      the pIXscTCR fusion protein incorporated in their capsid. Generated particles 
      specifically transduced melanoma cell lines expressing the HLA-A1/MAGE-A1 target 
      complex with at least 10-fold higher efficiency than control viruses. Whereas 
      loading of HLA-A1-positive cells with MAGE-A1 peptides leads to enhanced 
      transduction of the cells, the efficiency of virus transduction is strongly 
      reduced if the HLA-A1 molecules are not accessible at the target cell. Taken 
      together, these data provide proof of principle that pIXscTCR fusions can be used 
      to target HAdV-5 vectors to tumor cells expressing intracellular CT antigens.
FAU - de Vrij, J
AU  - de Vrij J
AD  - Department of Molecular Cell Biology, Leiden University Medical Center, Leiden, 
      The Netherlands.
FAU - Uil, T G
AU  - Uil TG
FAU - van den Hengel, S K
AU  - van den Hengel SK
FAU - Cramer, S J
AU  - Cramer SJ
FAU - Koppers-Lalic, D
AU  - Koppers-Lalic D
FAU - Verweij, M C
AU  - Verweij MC
FAU - Wiertz, E J H J
AU  - Wiertz EJ
FAU - Vellinga, J
AU  - Vellinga J
FAU - Willemsen, R A
AU  - Willemsen RA
FAU - Hoeben, R C
AU  - Hoeben RC
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080306
PL  - England
TA  - Gene Ther
JT  - Gene therapy
JID - 9421525
RN  - 0 (Antigens, Neoplasm)
RN  - 0 (Capsid Proteins)
RN  - 0 (HLA-A1 Antigen)
RN  - 0 (Melanoma-Specific Antigens)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (Receptors, Antigen, T-Cell)
SB  - IM
MH  - Adenoviridae/*genetics
MH  - Antigen Presentation
MH  - Antigens, Neoplasm/immunology
MH  - Capsid Proteins/genetics
MH  - Cell Line, Tumor
MH  - Cytotoxicity, Immunologic
MH  - Flow Cytometry
MH  - Gene Targeting
MH  - Genetic Engineering
MH  - Genetic Therapy/*methods
MH  - Genetic Vectors/*administration & dosage/genetics
MH  - HLA-A1 Antigen/immunology
MH  - Humans
MH  - Male
MH  - Melanoma/immunology/metabolism/*therapy
MH  - Melanoma-Specific Antigens
MH  - Neoplasm Proteins/immunology
MH  - Receptors, Antigen, T-Cell/genetics
MH  - Transduction, Genetic/*methods
EDAT- 2008/03/08 09:00
MHDA- 2008/09/17 09:00
CRDT- 2008/03/08 09:00
PHST- 2008/03/08 09:00 [pubmed]
PHST- 2008/09/17 09:00 [medline]
PHST- 2008/03/08 09:00 [entrez]
AID - gt200826 [pii]
AID - 10.1038/gt.2008.26 [doi]
PST - ppublish
SO  - Gene Ther. 2008 Jul;15(13):978-89. doi: 10.1038/gt.2008.26. Epub 2008 Mar 6.