PD-1 checkpoint inhibition enhances the antilymphoma activity of CD19-CAR-iNKT cells that retain their ability to prevent alloreactivity
Background Relapse and graft-versus-host disease (GVHD) are the main causes of death after allogeneic hematopoietic cell transplantation (HCT). Preclinical murine models and clinical data suggest that invariant natural killer T (iNKT) cells prevent acute and chronic GVHD. In addition, iNKT cells are...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article (Journal) |
| Language: | English |
| Published: |
March 20, 2024
|
| In: |
Journal for ImmunoTherapy of Cancer
Year: 2024, Volume: 12, Issue: 1, Pages: 1-13 |
| ISSN: | 2051-1426 |
| DOI: | 10.1136/jitc-2023-007829 |
| Online Access: | Verlag, kostenfrei, Volltext: https://doi.org/10.1136/jitc-2023-007829 Verlag, kostenfrei, Volltext: https://jitc.bmj.com/content/12/1/e007829 
|
| Author Notes: | Emmanuelle Moraes Ribeiro, Kathy-Ann Secker, Ana-Maria Nitulescu, Rebekka Schairer, Hildegard Keppeler, Anton Wesle, Hannes Schmid, Anita Schmitt, Brigitte Neuber, Daniela Chmiest, Silvia Podavini, Melanie Märklin, Boris Klimovich, Michael Schmitt, Fulya Korkmaz, Claudia Lengerke, Corina Schneidawind, Dominik Schneidawind |
MARC
| LEADER | 00000caa a2200000 c 4500 | ||
|---|---|---|---|
| 001 | 1891534416 | ||
| 003 | DE-627 | ||
| 005 | 20241205143145.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 240619s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1136/jitc-2023-007829 |2 doi | |
| 035 | |a (DE-627)1891534416 | ||
| 035 | |a (DE-599)KXP1891534416 | ||
| 035 | |a (OCoLC)1475299902 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rda | ||
| 041 | |a eng | ||
| 084 | |a 33 |2 sdnb | ||
| 100 | 1 | |a Moraes Ribeiro, Emmanuelle |e VerfasserIn |0 (DE-588)1333441819 |0 (DE-627)1891535412 |4 aut | |
| 245 | 1 | 0 | |a PD-1 checkpoint inhibition enhances the antilymphoma activity of CD19-CAR-iNKT cells that retain their ability to prevent alloreactivity |c Emmanuelle Moraes Ribeiro, Kathy-Ann Secker, Ana-Maria Nitulescu, Rebekka Schairer, Hildegard Keppeler, Anton Wesle, Hannes Schmid, Anita Schmitt, Brigitte Neuber, Daniela Chmiest, Silvia Podavini, Melanie Märklin, Boris Klimovich, Michael Schmitt, Fulya Korkmaz, Claudia Lengerke, Corina Schneidawind, Dominik Schneidawind |
| 264 | 1 | |c March 20, 2024 | |
| 300 | |b Illustrationen | ||
| 300 | |a 13 | ||
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Zuerst veröffentlicht: 31. Januar 2024 | ||
| 500 | |a Gesehen am 19.06.2024 | ||
| 520 | |a Background Relapse and graft-versus-host disease (GVHD) are the main causes of death after allogeneic hematopoietic cell transplantation (HCT). Preclinical murine models and clinical data suggest that invariant natural killer T (iNKT) cells prevent acute and chronic GVHD. In addition, iNKT cells are crucial for efficient immune responses against malignancies and contribute to reduced relapse rates after transplantation. Chimeric antigen receptors (CAR) redirect effector cells to cell surface antigens and enhance killing of target cells. With this study, we aimed to combine enhanced cytotoxicity of CD19-CAR-iNKT cells against lymphoma cells with their tolerogenic properties. - Methods iNKT cells were isolated from peripheral blood mononuclear cells and transduced with an anti-CD19-CAR retrovirus. After in vitro expansion, the functionality of CD19-CAR-iNKT cells was assessed by flow cytometry, image stream analysis and multiplex analysis in single-stimulation or repeated-stimulation assays. Moreover, the immunoregulatory properties of CD19-CAR-iNKT cells were analyzed in apoptosis assays and in mixed lymphocyte reactions. The effect of checkpoint inhibition through nivolumab was analyzed in these settings. - Results In this study, we could show that the cytotoxicity of CD19-CAR-iNKT cells was mediated either through engagement of their CAR or their invariant T-cell receptor, which may circumvent loss of response through antigen escape. However, encounter of CD19-CAR-iNKT cells with their target induced a phenotype of exhaustion. Consequently, checkpoint inhibition increased cytokine release, cytotoxicity and survival of CD19-CAR-iNKT cells. Additionally, they showed robust suppression of alloreactive immune responses. - Conclusion In this work, we demonstrate that CAR-iNKT cells are a powerful cytotherapeutic option to prevent or treat relapse while potentially reducing the risk of GVHD after allogeneic HCT. | ||
| 650 | 4 | |a Immune Checkpoint Inhibitors | |
| 650 | 4 | |a Immunotherapy | |
| 650 | 4 | |a Natural Killer T-Cells | |
| 650 | 4 | |a Receptors, Chimeric Antigen | |
| 650 | 4 | |a Transplantation Immunology | |
| 700 | 1 | |a Secker, Kathy-Ann |e VerfasserIn |4 aut | |
| 700 | 1 | |a Nitulescu, Ana-Maria |e VerfasserIn |4 aut | |
| 700 | 1 | |a Schairer, Rebekka |e VerfasserIn |4 aut | |
| 700 | 1 | |a Keppeler, Hildegard |e VerfasserIn |4 aut | |
| 700 | 1 | |a Wesle, Anton |e VerfasserIn |4 aut | |
| 700 | 1 | |a Schmid, Hannes |e VerfasserIn |4 aut | |
| 700 | 1 | |a Schmitt, Anita |d 1969- |e VerfasserIn |0 (DE-588)141722495 |0 (DE-627)630587752 |0 (DE-576)325593892 |4 aut | |
| 700 | 1 | |a Neuber, Brigitte |d 1974- |e VerfasserIn |0 (DE-588)1052913563 |0 (DE-627)789293188 |0 (DE-576)408653884 |4 aut | |
| 700 | 1 | |a Chmiest, Daniela |e VerfasserIn |4 aut | |
| 700 | 1 | |a Podavini, Silvia |e VerfasserIn |4 aut | |
| 700 | 1 | |a Märklin, Melanie |e VerfasserIn |4 aut | |
| 700 | 1 | |a Klimovich, Boris |e VerfasserIn |4 aut | |
| 700 | 1 | |a Schmitt, Michael |d 1966- |e VerfasserIn |0 (DE-588)133177173 |0 (DE-627)538000600 |0 (DE-576)299672921 |4 aut | |
| 700 | 1 | |a Korkmaz, Fulya |e VerfasserIn |4 aut | |
| 700 | 1 | |a Lengerke, Claudia |e VerfasserIn |4 aut | |
| 700 | 1 | |a Schneidawind, Corina |e VerfasserIn |4 aut | |
| 700 | 1 | |a Schneidawind, Dominik |e VerfasserIn |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Journal for ImmunoTherapy of Cancer |d London : BioMed Central, 2013 |g 12(2024), 1 vom: März, Artikel-ID e007829, Seite 1-13 |h Online-Ressource |w (DE-627)750086335 |w (DE-600)2719863-7 |w (DE-576)383767369 |x 2051-1426 |7 nnas |a PD-1 checkpoint inhibition enhances the antilymphoma activity of CD19-CAR-iNKT cells that retain their ability to prevent alloreactivity |
| 773 | 1 | 8 | |g volume:12 |g year:2024 |g number:1 |g month:03 |g elocationid:e007829 |g pages:1-13 |g extent:13 |a PD-1 checkpoint inhibition enhances the antilymphoma activity of CD19-CAR-iNKT cells that retain their ability to prevent alloreactivity |
| 856 | 4 | 0 | |u https://doi.org/10.1136/jitc-2023-007829 |x Verlag |x Resolving-System |z kostenfrei |3 Volltext |
| 856 | 4 | 0 | |u https://jitc.bmj.com/content/12/1/e007829 |x Verlag |z kostenfrei |3 Volltext |
| 951 | |a AR | ||
| 992 | |a 20240619 | ||
| 993 | |a Article | ||
| 994 | |a 2024 | ||
| 998 | |g 133177173 |a Schmitt, Michael |m 133177173:Schmitt, Michael |d 910000 |d 910100 |e 910000PS133177173 |e 910100PS133177173 |k 0/910000/ |k 1/910000/910100/ |p 14 | ||
| 998 | |g 1052913563 |a Neuber, Brigitte |m 1052913563:Neuber, Brigitte |d 910000 |d 910100 |e 910000PN1052913563 |e 910100PN1052913563 |k 0/910000/ |k 1/910000/910100/ |p 9 | ||
| 998 | |g 141722495 |a Schmitt, Anita |m 141722495:Schmitt, Anita |d 910000 |d 910100 |d 50000 |e 910000PS141722495 |e 910100PS141722495 |e 50000PS141722495 |k 0/910000/ |k 1/910000/910100/ |k 0/50000/ |p 8 | ||
| 999 | |a KXP-PPN1891534416 |e 453999719X | ||
| BIB | |a Y | ||
| SER | |a journal | ||
| JSO | |a {"person":[{"role":"aut","given":"Emmanuelle","family":"Moraes Ribeiro","display":"Moraes Ribeiro, Emmanuelle"},{"display":"Secker, Kathy-Ann","family":"Secker","given":"Kathy-Ann","role":"aut"},{"display":"Nitulescu, Ana-Maria","given":"Ana-Maria","role":"aut","family":"Nitulescu"},{"display":"Schairer, Rebekka","given":"Rebekka","role":"aut","family":"Schairer"},{"display":"Keppeler, Hildegard","family":"Keppeler","role":"aut","given":"Hildegard"},{"role":"aut","given":"Anton","family":"Wesle","display":"Wesle, Anton"},{"display":"Schmid, Hannes","role":"aut","given":"Hannes","family":"Schmid"},{"display":"Schmitt, Anita","family":"Schmitt","role":"aut","given":"Anita"},{"family":"Neuber","role":"aut","given":"Brigitte","display":"Neuber, Brigitte"},{"family":"Chmiest","role":"aut","given":"Daniela","display":"Chmiest, Daniela"},{"family":"Podavini","given":"Silvia","role":"aut","display":"Podavini, Silvia"},{"family":"Märklin","role":"aut","given":"Melanie","display":"Märklin, Melanie"},{"family":"Klimovich","given":"Boris","role":"aut","display":"Klimovich, Boris"},{"display":"Schmitt, Michael","role":"aut","given":"Michael","family":"Schmitt"},{"given":"Fulya","role":"aut","family":"Korkmaz","display":"Korkmaz, Fulya"},{"display":"Lengerke, Claudia","given":"Claudia","role":"aut","family":"Lengerke"},{"family":"Schneidawind","given":"Corina","role":"aut","display":"Schneidawind, Corina"},{"given":"Dominik","role":"aut","family":"Schneidawind","display":"Schneidawind, Dominik"}],"title":[{"title_sort":"PD-1 checkpoint inhibition enhances the antilymphoma activity of CD19-CAR-iNKT cells that retain their ability to prevent alloreactivity","title":"PD-1 checkpoint inhibition enhances the antilymphoma activity of CD19-CAR-iNKT cells that retain their ability to prevent alloreactivity"}],"language":["eng"],"physDesc":[{"noteIll":"Illustrationen","extent":"13 S."}],"type":{"bibl":"article-journal","media":"Online-Ressource"},"id":{"doi":["10.1136/jitc-2023-007829"],"eki":["1891534416"]},"origin":[{"dateIssuedKey":"2024","dateIssuedDisp":"March 20, 2024"}],"name":{"displayForm":["Emmanuelle Moraes Ribeiro, Kathy-Ann Secker, Ana-Maria Nitulescu, Rebekka Schairer, Hildegard Keppeler, Anton Wesle, Hannes Schmid, Anita Schmitt, Brigitte Neuber, Daniela Chmiest, Silvia Podavini, Melanie Märklin, Boris Klimovich, Michael Schmitt, Fulya Korkmaz, Claudia Lengerke, Corina Schneidawind, Dominik Schneidawind"]},"recId":"1891534416","note":["Zuerst veröffentlicht: 31. Januar 2024","Gesehen am 19.06.2024"],"relHost":[{"recId":"750086335","disp":"PD-1 checkpoint inhibition enhances the antilymphoma activity of CD19-CAR-iNKT cells that retain their ability to prevent alloreactivityJournal for ImmunoTherapy of Cancer","origin":[{"dateIssuedKey":"2013","publisher":"BioMed Central","dateIssuedDisp":"2013-","publisherPlace":"London"}],"id":{"zdb":["2719863-7"],"issn":["2051-1426"],"eki":["750086335"]},"part":{"extent":"13","text":"12(2024), 1 vom: März, Artikel-ID e007829, Seite 1-13","volume":"12","pages":"1-13","year":"2024","issue":"1"},"note":["Gesehen am 29.06.20"],"type":{"bibl":"periodical","media":"Online-Ressource"},"pubHistory":["1.2013 -"],"language":["eng"],"physDesc":[{"extent":"Online-Ressource"}],"title":[{"subtitle":"official journal of the Society for Immunotherapy of Cancer (SITC)","title":"Journal for ImmunoTherapy of Cancer","title_sort":"Journal for ImmunoTherapy of Cancer"}]}]} | ||
| SRT | |a MORAESRIBEPD1CHECKPO2020 | ||