PD1CD28 chimeric molecule enhances EGFRv⢠specific CAR-T cells in xenograft experiments in mouse models
Over the years, CAR-T cell therapy has achieved remarkable success in treating hematological malignancies. However, this efficacy has not been replicated in the context of glioblastoma (GBM). In this study, a PD1CD28 chimeric molecule was introduced into EGFRvâ¢-directed CAR-T cells, generating EGFR...
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| Veröffentlicht in: | PloS one 2024-10, Vol.19 (10), p.e0310430 |
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| creator | Chen, Wanqiong Xian, Na Zhao, Ningning Zhang, Qiong Xu, Yunlu |
| description | Over the years, CAR-T cell therapy has achieved remarkable success in treating hematological malignancies. However, this efficacy has not been replicated in the context of glioblastoma (GBM). In this study, a PD1CD28 chimeric molecule was introduced into EGFRvâ¢-directed CAR-T cells, generating EGFRvâ¢-P2A-PD1CD28 CAR-T cells. Notably, this modification significantly increased IL-2 secretion and enhanced antigen-dependent activation of CAR-T cells, especially when programmed cell death ligand 1 (PD-L1) was present in vitro. In addition, the in vivo xenograft experiments revealed that the PD1CD28 chimeric molecule played a pivotal role in reducing recurrence rates, effectively controlling recurrent tumor volume, and ultimately prolonging the survival of mice. Collectively, these findings suggest that EGFRvâ¢-directed CAR-T cells co-expressing the PD1CD28 chimeric molecule have the potential to significantly enhance the treatment efficacy against GBM. |
| doi_str_mv | 10.1371/journal.pone.0310430 |
| format | Article |
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Collectively, these findings suggest that EGFRvâ¢-directed CAR-T cells co-expressing the PD1CD28 chimeric molecule have the potential to significantly enhance the treatment efficacy against GBM.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0310430</identifier><language>eng</language><publisher>Public Library of Science</publisher><subject>Animal experimentation ; Antigens ; Apoptosis ; Care and treatment ; Glioblastoma multiforme ; Gliomas ; Patient outcomes ; T cells</subject><ispartof>PloS one, 2024-10, Vol.19 (10), p.e0310430</ispartof><rights>COPYRIGHT 2024 Public Library of Science</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,864,27924,27925</link.rule.ids></links><search><creatorcontrib>Chen, Wanqiong</creatorcontrib><creatorcontrib>Xian, Na</creatorcontrib><creatorcontrib>Zhao, Ningning</creatorcontrib><creatorcontrib>Zhang, Qiong</creatorcontrib><creatorcontrib>Xu, Yunlu</creatorcontrib><title>PD1CD28 chimeric molecule enhances EGFRv⢠specific CAR-T cells in xenograft experiments in mouse models</title><title>PloS one</title><description>Over the years, CAR-T cell therapy has achieved remarkable success in treating hematological malignancies. However, this efficacy has not been replicated in the context of glioblastoma (GBM). In this study, a PD1CD28 chimeric molecule was introduced into EGFRvâ¢-directed CAR-T cells, generating EGFRvâ¢-P2A-PD1CD28 CAR-T cells. Notably, this modification significantly increased IL-2 secretion and enhanced antigen-dependent activation of CAR-T cells, especially when programmed cell death ligand 1 (PD-L1) was present in vitro. In addition, the in vivo xenograft experiments revealed that the PD1CD28 chimeric molecule played a pivotal role in reducing recurrence rates, effectively controlling recurrent tumor volume, and ultimately prolonging the survival of mice. 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| source | DOAJ Directory of Open Access Journals; Public Library of Science (PLoS); EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Animal experimentation Antigens Apoptosis Care and treatment Glioblastoma multiforme Gliomas Patient outcomes T cells |
| title | PD1CD28 chimeric molecule enhances EGFRv⢠specific CAR-T cells in xenograft experiments in mouse models |
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