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231223s2005 xx ||||| 00| ||eng c |
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|a pubmed24n0510.xml
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|a (DE-627)NLM15300617X
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|a (NLM)15639645
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|a DE-627
|b ger
|c DE-627
|e rakwb
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041 |
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|a eng
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100 |
1 |
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|a Scholten, Kirsten B J
|e verfasserin
|4 aut
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245 |
1 |
0 |
|a Preservation and redirection of HPV16E7-specific T cell receptors for immunotherapy of cervical cancer
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264 |
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1 |
|c 2005
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336 |
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|a Text
|b txt
|2 rdacontent
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337 |
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|a ohne Hilfsmittel zu benutzen
|b n
|2 rdamedia
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338 |
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|a Band
|b nc
|2 rdacarrier
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500 |
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|a Date Completed 08.03.2005
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500 |
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|a Date Revised 18.11.2010
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500 |
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|a published: Print
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|a Citation Status MEDLINE
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520 |
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|a Human papilloma virus (HPV) type 16 infections of the genital tract are associated with the development of cervical cancer (CxCa) in women. HPV16-derived oncoproteins E6 and E7 are expressed constitutively in these lesions and might therefore be attractive candidates for T-cell-mediated adoptive immunotherapy. However, the low precursor frequency of HPV16E7-specific T cells in patients and healthy donors hampers routine isolation of these cells for adoptive transfer. To overcome this problem, we have isolated T cell receptor (TCR) genes from four different HPV16E7-specific healthy donor and patient-derived human cytotoxic T lymphocyte (CTL) clones. We examined whether genetic engineering of peripheral blood-derived CD8+ T cells in order to express HPV16E711-20-specific TCRs is feasible for adoptive transfer purposes. Reporter cells (Jurkat/MA) carrying a transgenic TCR were shown to bind relevant but not irrelevant tetramers. Moreover, these TCR-transgenic Jurkat/MA cells showed reactivity towards relevant target cells, indicating proper functional activity of the TCRs isolated from already available T cell clones. We next introduced an HPV16E711-20-specific TCR into blood-derived, CD8+ recipient T cells. Transgenic CTL clones stained positive for tetramers presenting the relevant HPV16E711-20 epitope and biological activity of the TCR in transduced CTL was confirmed by lytic activity and by interferon (IFN)-gamma secretion upon antigen-specific stimulation. Importantly, we show recognition of the endogenously processed and HLA-A2 presented HPV16E711-20 CTL epitope by A9-TCR-transgenic T cells. Collectively, our data indicate that HPV16E7 TCR gene transfer is feasible as an alternative strategy to generate human HPV16E7-specific T cells for the treatment of patients suffering from cervical cancer and other HPV16-induced malignancies
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650 |
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4 |
|a Journal Article
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650 |
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4 |
|a Research Support, Non-U.S. Gov't
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650 |
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7 |
|a Oncogene Proteins, Viral
|2 NLM
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650 |
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7 |
|a Papillomavirus E7 Proteins
|2 NLM
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650 |
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7 |
|a RNA, Viral
|2 NLM
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650 |
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7 |
|a Receptors, Antigen, T-Cell
|2 NLM
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650 |
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7 |
|a oncogene protein E7, Human papillomavirus type 16
|2 NLM
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700 |
1 |
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|a Schreurs, Marco W J
|e verfasserin
|4 aut
|
700 |
1 |
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|a Ruizendaal, Janneke J
|e verfasserin
|4 aut
|
700 |
1 |
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|a Kueter, Esther W M
|e verfasserin
|4 aut
|
700 |
1 |
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|a Kramer, Duco
|e verfasserin
|4 aut
|
700 |
1 |
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|a Veenbergen, Sharon
|e verfasserin
|4 aut
|
700 |
1 |
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|a Meijer, Chris J L M
|e verfasserin
|4 aut
|
700 |
1 |
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|a Hooijberg, Erik
|e verfasserin
|4 aut
|
773 |
0 |
8 |
|i Enthalten in
|t Clinical immunology (Orlando, Fla.)
|d 1999
|g 114(2005), 2 vom: 10. Feb., Seite 119-29
|w (DE-627)NLM098196855
|x 1521-7035
|7 nnns
|
773 |
1 |
8 |
|g volume:114
|g year:2005
|g number:2
|g day:10
|g month:02
|g pages:119-29
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912 |
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|a GBV_USEFLAG_A
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|a SYSFLAG_A
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912 |
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|a GBV_NLM
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912 |
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|a GBV_ILN_11
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912 |
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|a GBV_ILN_24
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912 |
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|a GBV_ILN_350
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951 |
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|a AR
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952 |
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|d 114
|j 2005
|e 2
|b 10
|c 02
|h 119-29
|