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T cells armed with the C-X-C chemokine receptor type 6 enhance adoptive cell therapy for pancreatic tumours

The efficacy of adoptive cell therapy for solid tumours is hampered by the poor accumulation of the transferred T cells in tumour tissue. Here, we show that the forced expression of the C-X-C chemokine receptor type 6 (CXCR6, whose ligand is highly expressed by human and murine pancreatic cancer cel...

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Autores principales: Lesch, Stefanie, Blumenberg, Viktoria, Stoiber, Stefan, Gottschlich, Adrian, Ogonek, Justyna, Cadilha, Bruno L., Dantes, Zahra, Rataj, Felicitas, Dorman, Klara, Lutz, Johannes, Karches, Clara H., Heise, Constanze, Kurzay, Mathias, Larimer, Benjamin M., Grassmann, Simon, Rapp, Moritz, Nottebrock, Alessia, Kruger, Stephan, Tokarew, Nicholas, Metzger, Philipp, Hoerth, Christine, Benmebarek, Mohamed-Reda, Dhoqina, Dario, Grünmeier, Ruth, Seifert, Matthias, Oener, Arman, Umut, Öykü, Joaquina, Sandy, Vimeux, Lene, Tran, Thi, Hank, Thomas, Baba, Taisuke, Huynh, Duc, Megens, Remco TA., Janssen, Klaus-Peter, Jastroch, Martin, Lamp, Daniel, Ruehland, Svenja, Di Pilato, Mauro, Pruessmann, Jasper N., Thomas, Moritz, Marr, Carsten, Ormanns, Steffen, Reischer, Anna, Hristov, Michael, Tartour, Eric, Donnadieu, Emmanuel, Rothenfusser, Simon, Duewell, Peter, König, Lars M., Schnurr, Max, Subklewe, Marion, Liss, Andrew S., Halama, Niels, Reichert, Maximilian, Mempel, Thorsten R., Endres, Stefan, Kobold, Sebastian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7611996/
https://www.ncbi.nlm.nih.gov/pubmed/34083764
http://dx.doi.org/10.1038/s41551-021-00737-6
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author Lesch, Stefanie
Blumenberg, Viktoria
Stoiber, Stefan
Gottschlich, Adrian
Ogonek, Justyna
Cadilha, Bruno L.
Dantes, Zahra
Rataj, Felicitas
Dorman, Klara
Lutz, Johannes
Karches, Clara H.
Heise, Constanze
Kurzay, Mathias
Larimer, Benjamin M.
Grassmann, Simon
Rapp, Moritz
Nottebrock, Alessia
Kruger, Stephan
Tokarew, Nicholas
Metzger, Philipp
Hoerth, Christine
Benmebarek, Mohamed-Reda
Dhoqina, Dario
Grünmeier, Ruth
Seifert, Matthias
Oener, Arman
Umut, Öykü
Joaquina, Sandy
Vimeux, Lene
Tran, Thi
Hank, Thomas
Baba, Taisuke
Huynh, Duc
Megens, Remco TA.
Janssen, Klaus-Peter
Jastroch, Martin
Lamp, Daniel
Ruehland, Svenja
Di Pilato, Mauro
Pruessmann, Jasper N.
Thomas, Moritz
Marr, Carsten
Ormanns, Steffen
Reischer, Anna
Hristov, Michael
Tartour, Eric
Donnadieu, Emmanuel
Rothenfusser, Simon
Duewell, Peter
König, Lars M.
Schnurr, Max
Subklewe, Marion
Liss, Andrew S.
Halama, Niels
Reichert, Maximilian
Mempel, Thorsten R.
Endres, Stefan
Kobold, Sebastian
author_facet Lesch, Stefanie
Blumenberg, Viktoria
Stoiber, Stefan
Gottschlich, Adrian
Ogonek, Justyna
Cadilha, Bruno L.
Dantes, Zahra
Rataj, Felicitas
Dorman, Klara
Lutz, Johannes
Karches, Clara H.
Heise, Constanze
Kurzay, Mathias
Larimer, Benjamin M.
Grassmann, Simon
Rapp, Moritz
Nottebrock, Alessia
Kruger, Stephan
Tokarew, Nicholas
Metzger, Philipp
Hoerth, Christine
Benmebarek, Mohamed-Reda
Dhoqina, Dario
Grünmeier, Ruth
Seifert, Matthias
Oener, Arman
Umut, Öykü
Joaquina, Sandy
Vimeux, Lene
Tran, Thi
Hank, Thomas
Baba, Taisuke
Huynh, Duc
Megens, Remco TA.
Janssen, Klaus-Peter
Jastroch, Martin
Lamp, Daniel
Ruehland, Svenja
Di Pilato, Mauro
Pruessmann, Jasper N.
Thomas, Moritz
Marr, Carsten
Ormanns, Steffen
Reischer, Anna
Hristov, Michael
Tartour, Eric
Donnadieu, Emmanuel
Rothenfusser, Simon
Duewell, Peter
König, Lars M.
Schnurr, Max
Subklewe, Marion
Liss, Andrew S.
Halama, Niels
Reichert, Maximilian
Mempel, Thorsten R.
Endres, Stefan
Kobold, Sebastian
author_sort Lesch, Stefanie
collection PubMed
description The efficacy of adoptive cell therapy for solid tumours is hampered by the poor accumulation of the transferred T cells in tumour tissue. Here, we show that the forced expression of the C-X-C chemokine receptor type 6 (CXCR6, whose ligand is highly expressed by human and murine pancreatic cancer cells and by tumour-infiltrating immune cells) in antigen-specific T cells enhanced the recognition and lysis of pancreatic cancer cells and the efficacy of adoptive cell therapy for pancreatic cancer. In mice with subcutaneous pancreatic tumours treated with T cells with either a transgenic T-cell receptor or a murine chimeric antigen receptor targeting the tumour-associated antigen epithelial cell-adhesion molecule, and in mice with orthotopic pancreatic tumours or patient-derived xenografts treated with T cells expressing a chimeric antigen receptor targeting mesothelin, the T cells exhibited enhanced intratumoral accumulation, exerted sustained antitumoral activity and prolonged animal survival only when co-expressing CXCR6. Arming tumour-specific T cells with tumour-specific chemokine receptors may represent a promising strategy for the realization of adoptive cell therapy for solid tumours.
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spelling pubmed-76119962021-12-03 T cells armed with the C-X-C chemokine receptor type 6 enhance adoptive cell therapy for pancreatic tumours Lesch, Stefanie Blumenberg, Viktoria Stoiber, Stefan Gottschlich, Adrian Ogonek, Justyna Cadilha, Bruno L. Dantes, Zahra Rataj, Felicitas Dorman, Klara Lutz, Johannes Karches, Clara H. Heise, Constanze Kurzay, Mathias Larimer, Benjamin M. Grassmann, Simon Rapp, Moritz Nottebrock, Alessia Kruger, Stephan Tokarew, Nicholas Metzger, Philipp Hoerth, Christine Benmebarek, Mohamed-Reda Dhoqina, Dario Grünmeier, Ruth Seifert, Matthias Oener, Arman Umut, Öykü Joaquina, Sandy Vimeux, Lene Tran, Thi Hank, Thomas Baba, Taisuke Huynh, Duc Megens, Remco TA. Janssen, Klaus-Peter Jastroch, Martin Lamp, Daniel Ruehland, Svenja Di Pilato, Mauro Pruessmann, Jasper N. Thomas, Moritz Marr, Carsten Ormanns, Steffen Reischer, Anna Hristov, Michael Tartour, Eric Donnadieu, Emmanuel Rothenfusser, Simon Duewell, Peter König, Lars M. Schnurr, Max Subklewe, Marion Liss, Andrew S. Halama, Niels Reichert, Maximilian Mempel, Thorsten R. Endres, Stefan Kobold, Sebastian Nat Biomed Eng Article The efficacy of adoptive cell therapy for solid tumours is hampered by the poor accumulation of the transferred T cells in tumour tissue. Here, we show that the forced expression of the C-X-C chemokine receptor type 6 (CXCR6, whose ligand is highly expressed by human and murine pancreatic cancer cells and by tumour-infiltrating immune cells) in antigen-specific T cells enhanced the recognition and lysis of pancreatic cancer cells and the efficacy of adoptive cell therapy for pancreatic cancer. In mice with subcutaneous pancreatic tumours treated with T cells with either a transgenic T-cell receptor or a murine chimeric antigen receptor targeting the tumour-associated antigen epithelial cell-adhesion molecule, and in mice with orthotopic pancreatic tumours or patient-derived xenografts treated with T cells expressing a chimeric antigen receptor targeting mesothelin, the T cells exhibited enhanced intratumoral accumulation, exerted sustained antitumoral activity and prolonged animal survival only when co-expressing CXCR6. Arming tumour-specific T cells with tumour-specific chemokine receptors may represent a promising strategy for the realization of adoptive cell therapy for solid tumours. 2021-11-01 2021-06-03 /pmc/articles/PMC7611996/ /pubmed/34083764 http://dx.doi.org/10.1038/s41551-021-00737-6 Text en http://www.nature.com/authors/editorial_policies/license.html#termsUsers may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Lesch, Stefanie
Blumenberg, Viktoria
Stoiber, Stefan
Gottschlich, Adrian
Ogonek, Justyna
Cadilha, Bruno L.
Dantes, Zahra
Rataj, Felicitas
Dorman, Klara
Lutz, Johannes
Karches, Clara H.
Heise, Constanze
Kurzay, Mathias
Larimer, Benjamin M.
Grassmann, Simon
Rapp, Moritz
Nottebrock, Alessia
Kruger, Stephan
Tokarew, Nicholas
Metzger, Philipp
Hoerth, Christine
Benmebarek, Mohamed-Reda
Dhoqina, Dario
Grünmeier, Ruth
Seifert, Matthias
Oener, Arman
Umut, Öykü
Joaquina, Sandy
Vimeux, Lene
Tran, Thi
Hank, Thomas
Baba, Taisuke
Huynh, Duc
Megens, Remco TA.
Janssen, Klaus-Peter
Jastroch, Martin
Lamp, Daniel
Ruehland, Svenja
Di Pilato, Mauro
Pruessmann, Jasper N.
Thomas, Moritz
Marr, Carsten
Ormanns, Steffen
Reischer, Anna
Hristov, Michael
Tartour, Eric
Donnadieu, Emmanuel
Rothenfusser, Simon
Duewell, Peter
König, Lars M.
Schnurr, Max
Subklewe, Marion
Liss, Andrew S.
Halama, Niels
Reichert, Maximilian
Mempel, Thorsten R.
Endres, Stefan
Kobold, Sebastian
T cells armed with the C-X-C chemokine receptor type 6 enhance adoptive cell therapy for pancreatic tumours
title T cells armed with the C-X-C chemokine receptor type 6 enhance adoptive cell therapy for pancreatic tumours
title_full T cells armed with the C-X-C chemokine receptor type 6 enhance adoptive cell therapy for pancreatic tumours
title_fullStr T cells armed with the C-X-C chemokine receptor type 6 enhance adoptive cell therapy for pancreatic tumours
title_full_unstemmed T cells armed with the C-X-C chemokine receptor type 6 enhance adoptive cell therapy for pancreatic tumours
title_short T cells armed with the C-X-C chemokine receptor type 6 enhance adoptive cell therapy for pancreatic tumours
title_sort t cells armed with the c-x-c chemokine receptor type 6 enhance adoptive cell therapy for pancreatic tumours
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7611996/
https://www.ncbi.nlm.nih.gov/pubmed/34083764
http://dx.doi.org/10.1038/s41551-021-00737-6
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