Allogeneic CAR Invariant Natural Killer T Cells Exert Potent Antitumor Effects through Host CD8 T-Cell Cross-Priming
©2021 The Authors; Published by the American Association for Cancer Research..
PURPOSE: The development of allogeneic chimeric antigen receptor (CAR) T-cell therapies for off-the-shelf use is a major goal that faces two main immunologic challenges, namely the risk of graft-versus-host disease (GvHD) induction by the transferred cells and the rejection by the host immune system limiting their persistence. In this work we assessed the direct and indirect antitumor effect of allogeneic CAR-engineered invariant natural killer T (iNKT) cells, a cell population without GvHD-induction potential that displays immunomodulatory properties.
EXPERIMENTAL DESIGN: After assessing murine CAR iNKT cells direct antitumor effects in vitro and in vivo, we employed an immunocompetent mouse model of B-cell lymphoma to assess the interaction between allogeneic CAR iNKT cells and endogenous immune cells.
RESULTS: We demonstrate that allogeneic CAR iNKT cells exerted potent direct and indirect antitumor activity when administered across major MHC barriers by inducing tumor-specific antitumor immunity through host CD8 T-cell cross-priming.
CONCLUSIONS: In addition to their known direct cytotoxic effect, allogeneic CAR iNKT cells induce host CD8 T-cell antitumor responses, resulting in a potent antitumor effect lasting longer than the physical persistence of the allogeneic cells. The utilization of off-the-shelf allogeneic CAR iNKT cells could meet significant unmet needs in the clinic.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:27 |
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| Enthalten in: |
Clinical cancer research : an official journal of the American Association for Cancer Research - 27(2021), 21 vom: 01. Nov., Seite 6054-6064 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Simonetta, Federico [VerfasserIn] |
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| Links: |
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| Themen: |
Journal Article |
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| Anmerkungen: |
Date Completed 31.03.2022 Date Revised 11.02.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1158/1078-0432.CCR-21-1329 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM329205099 |
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| 245 | 1 | 0 | |a Allogeneic CAR Invariant Natural Killer T Cells Exert Potent Antitumor Effects through Host CD8 T-Cell Cross-Priming |
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| 500 | |a Date Revised 11.02.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a ©2021 The Authors; Published by the American Association for Cancer Research. | ||
| 520 | |a PURPOSE: The development of allogeneic chimeric antigen receptor (CAR) T-cell therapies for off-the-shelf use is a major goal that faces two main immunologic challenges, namely the risk of graft-versus-host disease (GvHD) induction by the transferred cells and the rejection by the host immune system limiting their persistence. In this work we assessed the direct and indirect antitumor effect of allogeneic CAR-engineered invariant natural killer T (iNKT) cells, a cell population without GvHD-induction potential that displays immunomodulatory properties | ||
| 520 | |a EXPERIMENTAL DESIGN: After assessing murine CAR iNKT cells direct antitumor effects in vitro and in vivo, we employed an immunocompetent mouse model of B-cell lymphoma to assess the interaction between allogeneic CAR iNKT cells and endogenous immune cells | ||
| 520 | |a RESULTS: We demonstrate that allogeneic CAR iNKT cells exerted potent direct and indirect antitumor activity when administered across major MHC barriers by inducing tumor-specific antitumor immunity through host CD8 T-cell cross-priming | ||
| 520 | |a CONCLUSIONS: In addition to their known direct cytotoxic effect, allogeneic CAR iNKT cells induce host CD8 T-cell antitumor responses, resulting in a potent antitumor effect lasting longer than the physical persistence of the allogeneic cells. The utilization of off-the-shelf allogeneic CAR iNKT cells could meet significant unmet needs in the clinic | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 700 | 1 | |a Lohmeyer, Juliane K |e verfasserin |4 aut | |
| 700 | 1 | |a Hirai, Toshihito |e verfasserin |4 aut | |
| 700 | 1 | |a Maas-Bauer, Kristina |e verfasserin |4 aut | |
| 700 | 1 | |a Alvarez, Maite |e verfasserin |4 aut | |
| 700 | 1 | |a Wenokur, Arielle S |e verfasserin |4 aut | |
| 700 | 1 | |a Baker, Jeanette |e verfasserin |4 aut | |
| 700 | 1 | |a Aalipour, Amin |e verfasserin |4 aut | |
| 700 | 1 | |a Ji, Xuhuai |e verfasserin |4 aut | |
| 700 | 1 | |a Haile, Samuel |e verfasserin |4 aut | |
| 700 | 1 | |a Mackall, Crystal L |e verfasserin |4 aut | |
| 700 | 1 | |a Negrin, Robert S |e verfasserin |4 aut | |
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