Academic Journal
CAR T cells as micropharmacies against solid cancers: Combining effector T-cell mediated cell death with vascular targeting in a one-step engineering process
| العنوان: | CAR T cells as micropharmacies against solid cancers: Combining effector T-cell mediated cell death with vascular targeting in a one-step engineering process |
|---|---|
| المؤلفون: | Altvater, Bianca, Kailayangiri, Sareetha, Spurny, Christian, Flügge, Maike, Meltzer, Jutta, Greune, Lea, Urban, Katja, Schwöppe, Christian, Brand, Caroline, Schliemann, Christoph, Hintelmann, Heike, Harrach, Saliha, Hartmann, Wolfgang, Abken, Hinrich, Kuehle, Johannes, Schambach, Axel, Görlich, Dennis, Berdel, Wolfgang E., Rossig, Claudia |
| المساهمون: | Deutsche Forschungsgemeinschaft |
| المصدر: | Cancer Gene Therapy ; volume 30, issue 10, page 1355-1368 ; ISSN 0929-1903 1476-5500 |
| بيانات النشر: | Springer Science and Business Media LLC |
| سنة النشر: | 2023 |
| الوصف: | To enhance the potency of chimeric antigen receptor (CAR) engineered T cells in solid cancers, we designed a novel cell-based combination strategy with an additional therapeutic mode of action. CAR T cells are used as micropharmacies to produce a targeted pro-coagulatory fusion protein, truncated tissue factor (tTF)-NGR, which exerts pro-coagulatory activity and hypoxia upon relocalization to the vascular endothelial cells that invade tumor tissues. Delivery by CAR T cells aimed to induce locoregional tumor vascular infarction for combined immune-mediated and hypoxic tumor cell death. Human T cells that were one-vector gene-modified to express a G D2 -specific CAR along with CAR-inducible tTF-NGR exerted potent G D2 -specific effector functions while secreting tTF-NGR that activates the extrinsic coagulation pathway in a strictly G D2 -dependent manner. In murine models, the CAR T cells infiltrated G D2 -positive tumor xenografts, secreted tTF-NGR into the tumor microenvironment and showed a trend towards superior therapeutic activity compared with control cells producing functionally inactive tTF-NGR. In vitro evidence supports a mechanism of hypoxia-mediated enhancement of T cell cytolytic activity. We conclude that combined CAR T cell targeting with an additional mechanism of antitumor action in a one-vector engineering strategy is a promising approach to be further developed for targeted treatment of solid cancers. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1038/s41417-023-00642-x |
| الاتاحة: | http://dx.doi.org/10.1038/s41417-023-00642-x https://www.nature.com/articles/s41417-023-00642-x.pdf https://www.nature.com/articles/s41417-023-00642-x |
| Rights: | https://creativecommons.org/licenses/by/4.0 ; https://creativecommons.org/licenses/by/4.0 |
| رقم الانضمام: | edsbas.90E0B72A |
| قاعدة البيانات: | BASE |
| ResultId |
1 |
|---|---|
| Header |
edsbas BASE edsbas.90E0B72A 961 3 Academic Journal academicJournal 960.976379394531 |
| PLink |
https://search.ebscohost.com/login.aspx?direct=true&site=eds-live&scope=site&db=edsbas&AN=edsbas.90E0B72A&custid=s6537998&authtype=sso |
| FullText |
Array
(
[Availability] => 0
)
Array ( [0] => Array ( [Url] => http://dx.doi.org/10.1038/s41417-023-00642-x# [Name] => EDS - BASE [Category] => fullText [Text] => View record in BASE [MouseOverText] => View record in BASE ) ) |
| Items |
Array
(
[Name] => Title
[Label] => Title
[Group] => Ti
[Data] => CAR T cells as micropharmacies against solid cancers: Combining effector T-cell mediated cell death with vascular targeting in a one-step engineering process
)
Array ( [Name] => Author [Label] => Authors [Group] => Au [Data] => <searchLink fieldCode="AR" term="%22Altvater%2C+Bianca%22">Altvater, Bianca</searchLink><br /><searchLink fieldCode="AR" term="%22Kailayangiri%2C+Sareetha%22">Kailayangiri, Sareetha</searchLink><br /><searchLink fieldCode="AR" term="%22Spurny%2C+Christian%22">Spurny, Christian</searchLink><br /><searchLink fieldCode="AR" term="%22Flügge%2C+Maike%22">Flügge, Maike</searchLink><br /><searchLink fieldCode="AR" term="%22Meltzer%2C+Jutta%22">Meltzer, Jutta</searchLink><br /><searchLink fieldCode="AR" term="%22Greune%2C+Lea%22">Greune, Lea</searchLink><br /><searchLink fieldCode="AR" term="%22Urban%2C+Katja%22">Urban, Katja</searchLink><br /><searchLink fieldCode="AR" term="%22Schwöppe%2C+Christian%22">Schwöppe, Christian</searchLink><br /><searchLink fieldCode="AR" term="%22Brand%2C+Caroline%22">Brand, Caroline</searchLink><br /><searchLink fieldCode="AR" term="%22Schliemann%2C+Christoph%22">Schliemann, Christoph</searchLink><br /><searchLink fieldCode="AR" term="%22Hintelmann%2C+Heike%22">Hintelmann, Heike</searchLink><br /><searchLink fieldCode="AR" term="%22Harrach%2C+Saliha%22">Harrach, Saliha</searchLink><br /><searchLink fieldCode="AR" term="%22Hartmann%2C+Wolfgang%22">Hartmann, Wolfgang</searchLink><br /><searchLink fieldCode="AR" term="%22Abken%2C+Hinrich%22">Abken, Hinrich</searchLink><br /><searchLink fieldCode="AR" term="%22Kuehle%2C+Johannes%22">Kuehle, Johannes</searchLink><br /><searchLink fieldCode="AR" term="%22Schambach%2C+Axel%22">Schambach, Axel</searchLink><br /><searchLink fieldCode="AR" term="%22Görlich%2C+Dennis%22">Görlich, Dennis</searchLink><br /><searchLink fieldCode="AR" term="%22Berdel%2C+Wolfgang+E%2E%22">Berdel, Wolfgang E.</searchLink><br /><searchLink fieldCode="AR" term="%22Rossig%2C+Claudia%22">Rossig, Claudia</searchLink> ) Array ( [Name] => Author [Label] => Contributors [Group] => Au [Data] => Deutsche Forschungsgemeinschaft ) Array ( [Name] => TitleSource [Label] => Source [Group] => Src [Data] => Cancer Gene Therapy ; volume 30, issue 10, page 1355-1368 ; ISSN 0929-1903 1476-5500 ) Array ( [Name] => Publisher [Label] => Publisher Information [Group] => PubInfo [Data] => Springer Science and Business Media LLC ) Array ( [Name] => DatePubCY [Label] => Publication Year [Group] => Date [Data] => 2023 ) Array ( [Name] => Abstract [Label] => Description [Group] => Ab [Data] => To enhance the potency of chimeric antigen receptor (CAR) engineered T cells in solid cancers, we designed a novel cell-based combination strategy with an additional therapeutic mode of action. CAR T cells are used as micropharmacies to produce a targeted pro-coagulatory fusion protein, truncated tissue factor (tTF)-NGR, which exerts pro-coagulatory activity and hypoxia upon relocalization to the vascular endothelial cells that invade tumor tissues. Delivery by CAR T cells aimed to induce locoregional tumor vascular infarction for combined immune-mediated and hypoxic tumor cell death. Human T cells that were one-vector gene-modified to express a G D2 -specific CAR along with CAR-inducible tTF-NGR exerted potent G D2 -specific effector functions while secreting tTF-NGR that activates the extrinsic coagulation pathway in a strictly G D2 -dependent manner. In murine models, the CAR T cells infiltrated G D2 -positive tumor xenografts, secreted tTF-NGR into the tumor microenvironment and showed a trend towards superior therapeutic activity compared with control cells producing functionally inactive tTF-NGR. In vitro evidence supports a mechanism of hypoxia-mediated enhancement of T cell cytolytic activity. We conclude that combined CAR T cell targeting with an additional mechanism of antitumor action in a one-vector engineering strategy is a promising approach to be further developed for targeted treatment of solid cancers. ) Array ( [Name] => TypeDocument [Label] => Document Type [Group] => TypDoc [Data] => article in journal/newspaper ) Array ( [Name] => Language [Label] => Language [Group] => Lang [Data] => English ) Array ( [Name] => DOI [Label] => DOI [Group] => ID [Data] => 10.1038/s41417-023-00642-x ) Array ( [Name] => URL [Label] => Availability [Group] => URL [Data] => http://dx.doi.org/10.1038/s41417-023-00642-x<br />https://www.nature.com/articles/s41417-023-00642-x.pdf<br />https://www.nature.com/articles/s41417-023-00642-x ) Array ( [Name] => Copyright [Label] => Rights [Group] => Cpyrght [Data] => https://creativecommons.org/licenses/by/4.0 ; https://creativecommons.org/licenses/by/4.0 ) Array ( [Name] => AN [Label] => Accession Number [Group] => ID [Data] => edsbas.90E0B72A ) |
| RecordInfo |
Array
(
[BibEntity] => Array
(
[Identifiers] => Array
(
[0] => Array
(
[Type] => doi
[Value] => 10.1038/s41417-023-00642-x
)
)
[Languages] => Array
(
[0] => Array
(
[Text] => English
)
)
[Titles] => Array
(
[0] => Array
(
[TitleFull] => CAR T cells as micropharmacies against solid cancers: Combining effector T-cell mediated cell death with vascular targeting in a one-step engineering process
[Type] => main
)
)
)
[BibRelationships] => Array
(
[HasContributorRelationships] => Array
(
[0] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Altvater, Bianca
)
)
)
[1] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Kailayangiri, Sareetha
)
)
)
[2] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Spurny, Christian
)
)
)
[3] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Flügge, Maike
)
)
)
[4] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Meltzer, Jutta
)
)
)
[5] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Greune, Lea
)
)
)
[6] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Urban, Katja
)
)
)
[7] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Schwöppe, Christian
)
)
)
[8] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Brand, Caroline
)
)
)
[9] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Schliemann, Christoph
)
)
)
[10] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Hintelmann, Heike
)
)
)
[11] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Harrach, Saliha
)
)
)
[12] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Hartmann, Wolfgang
)
)
)
[13] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Abken, Hinrich
)
)
)
[14] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Kuehle, Johannes
)
)
)
[15] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Schambach, Axel
)
)
)
[16] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Görlich, Dennis
)
)
)
[17] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Berdel, Wolfgang E.
)
)
)
[18] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Rossig, Claudia
)
)
)
[19] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Deutsche Forschungsgemeinschaft
)
)
)
)
[IsPartOfRelationships] => Array
(
[0] => Array
(
[BibEntity] => Array
(
[Dates] => Array
(
[0] => Array
(
[D] => 01
[M] => 01
[Type] => published
[Y] => 2023
)
)
[Identifiers] => Array
(
[0] => Array
(
[Type] => issn-locals
[Value] => edsbas
)
[1] => Array
(
[Type] => issn-locals
[Value] => edsbas.oa
)
)
[Titles] => Array
(
[0] => Array
(
[TitleFull] => Cancer Gene Therapy ; volume 30, issue 10, page 1355-1368 ; ISSN 0929-1903 1476-5500
[Type] => main
)
)
)
)
)
)
)
|
| IllustrationInfo |