Preservation and redirection of HPV16E7-specific T cell receptors for immunotherapy of cervical cancer

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 imm...

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Veröffentlicht in:Clinical immunology (Orlando, Fla.). - 1999. - 114(2005), 2 vom: 10. Feb., Seite 119-29
1. Verfasser: Scholten, Kirsten B J (VerfasserIn)
Weitere Verfasser: Schreurs, Marco W J, Ruizendaal, Janneke J, Kueter, Esther W M, Kramer, Duco, Veenbergen, Sharon, Meijer, Chris J L M, Hooijberg, Erik
Format: Aufsatz
Sprache:English
Veröffentlicht: 2005
Zugriff auf das übergeordnete Werk:Clinical immunology (Orlando, Fla.)
Schlagworte:Journal Article Research Support, Non-U.S. Gov't Oncogene Proteins, Viral Papillomavirus E7 Proteins RNA, Viral Receptors, Antigen, T-Cell oncogene protein E7, Human papillomavirus type 16
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100 1 |a Scholten, Kirsten B J  |e verfasserin  |4 aut 
245 1 0 |a Preservation and redirection of HPV16E7-specific T cell receptors for immunotherapy of cervical cancer 
264 1 |c 2005 
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520 |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 
650 4 |a Journal Article 
650 4 |a Research Support, Non-U.S. Gov't 
650 7 |a Oncogene Proteins, Viral  |2 NLM 
650 7 |a Papillomavirus E7 Proteins  |2 NLM 
650 7 |a RNA, Viral  |2 NLM 
650 7 |a Receptors, Antigen, T-Cell  |2 NLM 
650 7 |a oncogene protein E7, Human papillomavirus type 16  |2 NLM 
700 1 |a Schreurs, Marco W J  |e verfasserin  |4 aut 
700 1 |a Ruizendaal, Janneke J  |e verfasserin  |4 aut 
700 1 |a Kueter, Esther W M  |e verfasserin  |4 aut 
700 1 |a Kramer, Duco  |e verfasserin  |4 aut 
700 1 |a Veenbergen, Sharon  |e verfasserin  |4 aut 
700 1 |a Meijer, Chris J L M  |e verfasserin  |4 aut 
700 1 |a Hooijberg, Erik  |e verfasserin  |4 aut 
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