Novel scFv against Notch Ligand JAG1 Suitable for Development of Cell Therapies toward JAG1-Positive Tumors
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2023 |
| Outros Autores: | , , , , , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
| Texto Completo: | http://hdl.handle.net/10362/158554 |
Resumo: | Funding Information: This research was funded by the Fundação para a Ciência e Tecnologia/Ministério da Ciência, Tecnologia e Ensino Superior (FCT/MCTES, Portugal) grant PTDC/BBB-BMD/4497/2014 (to A.B.), through national funds to iNOVA4Health (UIDB/04462/2020 and UIDP/04462/2020), and the Associate Laboratory LS4FUTURE (LA/P/0087/2020). Publisher Copyright: © 2023 by the authors. |
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Novel scFv against Notch Ligand JAG1 Suitable for Development of Cell Therapies toward JAG1-Positive Tumorscell therapychimeric antigen receptorcytotoxic activityJAG1Notch signalingsingle-chain variable fragmentBiochemistryMolecular BiologySDG 3 - Good Health and Well-beingFunding Information: This research was funded by the Fundação para a Ciência e Tecnologia/Ministério da Ciência, Tecnologia e Ensino Superior (FCT/MCTES, Portugal) grant PTDC/BBB-BMD/4497/2014 (to A.B.), through national funds to iNOVA4Health (UIDB/04462/2020 and UIDP/04462/2020), and the Associate Laboratory LS4FUTURE (LA/P/0087/2020). Publisher Copyright: © 2023 by the authors.The Notch signaling ligand JAG1 is overexpressed in various aggressive tumors and is associated with poor clinical prognosis. Hence, therapies targeting oncogenic JAG1 hold great potential for the treatment of certain tumors. Here, we report the identification of specific anti-JAG1 single-chain variable fragments (scFvs), one of them endowing chimeric antigen receptor (CAR) T cells with cytotoxicity against JAG1-positive cells. Anti-JAG1 scFvs were identified from human phage display libraries, reformatted into full-length monoclonal antibodies (Abs), and produced in mammalian cells. The characterization of these Abs identified two specific anti-JAG1 Abs (J1.B5 and J1.F1) with nanomolar affinities. Cloning the respective scFv sequences in our second- and third-generation CAR backbones resulted in six anti-JAG1 CAR constructs, which were screened for JAG1-mediated T-cell activation in Jurkat T cells in coculture assays with JAG1-positive cell lines. Studies in primary T cells demonstrated that one CAR harboring the J1.B5 scFv significantly induced effective T-cell activation in the presence of JAG1-positive, but not in JAG1-knockout, cancer cells, and enabled specific killing of JAG1-positive cells. Thus, this new anti-JAG1 scFv represents a promising candidate for the development of cell therapies against JAG1-positive tumors.Instituto de Tecnologia Química e Biológica António Xavier (ITQB)RUNSilva, GabrielaRodrigues, Ana F.Ferreira, SusanaMatos, CarolinaEleutério, Rute P.Marques, GonçaloKucheryava, KhrystynaLemos, Ana R.Sousa, Pedro M.F.Castro, RuteBarbas, AnaSimão, DanielAlves, Paula M.2023-09-30T22:22:26Z2023-032023-03-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10362/158554eng2218-273XPURE: 72699971https://doi.org/10.3390/biom13030459info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-03-11T05:41:06Zoai:run.unl.pt:10362/158554Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:57:12.852678Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
| dc.title.none.fl_str_mv |
Novel scFv against Notch Ligand JAG1 Suitable for Development of Cell Therapies toward JAG1-Positive Tumors |
| title |
Novel scFv against Notch Ligand JAG1 Suitable for Development of Cell Therapies toward JAG1-Positive Tumors |
| spellingShingle |
Novel scFv against Notch Ligand JAG1 Suitable for Development of Cell Therapies toward JAG1-Positive Tumors Silva, Gabriela cell therapy chimeric antigen receptor cytotoxic activity JAG1 Notch signaling single-chain variable fragment Biochemistry Molecular Biology SDG 3 - Good Health and Well-being |
| title_short |
Novel scFv against Notch Ligand JAG1 Suitable for Development of Cell Therapies toward JAG1-Positive Tumors |
| title_full |
Novel scFv against Notch Ligand JAG1 Suitable for Development of Cell Therapies toward JAG1-Positive Tumors |
| title_fullStr |
Novel scFv against Notch Ligand JAG1 Suitable for Development of Cell Therapies toward JAG1-Positive Tumors |
| title_full_unstemmed |
Novel scFv against Notch Ligand JAG1 Suitable for Development of Cell Therapies toward JAG1-Positive Tumors |
| title_sort |
Novel scFv against Notch Ligand JAG1 Suitable for Development of Cell Therapies toward JAG1-Positive Tumors |
| author |
Silva, Gabriela |
| author_facet |
Silva, Gabriela Rodrigues, Ana F. Ferreira, Susana Matos, Carolina Eleutério, Rute P. Marques, Gonçalo Kucheryava, Khrystyna Lemos, Ana R. Sousa, Pedro M.F. Castro, Rute Barbas, Ana Simão, Daniel Alves, Paula M. |
| author_role |
author |
| author2 |
Rodrigues, Ana F. Ferreira, Susana Matos, Carolina Eleutério, Rute P. Marques, Gonçalo Kucheryava, Khrystyna Lemos, Ana R. Sousa, Pedro M.F. Castro, Rute Barbas, Ana Simão, Daniel Alves, Paula M. |
| author2_role |
author author author author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
Instituto de Tecnologia Química e Biológica António Xavier (ITQB) RUN |
| dc.contributor.author.fl_str_mv |
Silva, Gabriela Rodrigues, Ana F. Ferreira, Susana Matos, Carolina Eleutério, Rute P. Marques, Gonçalo Kucheryava, Khrystyna Lemos, Ana R. Sousa, Pedro M.F. Castro, Rute Barbas, Ana Simão, Daniel Alves, Paula M. |
| dc.subject.por.fl_str_mv |
cell therapy chimeric antigen receptor cytotoxic activity JAG1 Notch signaling single-chain variable fragment Biochemistry Molecular Biology SDG 3 - Good Health and Well-being |
| topic |
cell therapy chimeric antigen receptor cytotoxic activity JAG1 Notch signaling single-chain variable fragment Biochemistry Molecular Biology SDG 3 - Good Health and Well-being |
| description |
Funding Information: This research was funded by the Fundação para a Ciência e Tecnologia/Ministério da Ciência, Tecnologia e Ensino Superior (FCT/MCTES, Portugal) grant PTDC/BBB-BMD/4497/2014 (to A.B.), through national funds to iNOVA4Health (UIDB/04462/2020 and UIDP/04462/2020), and the Associate Laboratory LS4FUTURE (LA/P/0087/2020). Publisher Copyright: © 2023 by the authors. |
| publishDate |
2023 |
| dc.date.none.fl_str_mv |
2023-09-30T22:22:26Z 2023-03 2023-03-01T00:00:00Z |
| dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
| format |
article |
| status_str |
publishedVersion |
| dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10362/158554 |
| url |
http://hdl.handle.net/10362/158554 |
| dc.language.iso.fl_str_mv |
eng |
| language |
eng |
| dc.relation.none.fl_str_mv |
2218-273X PURE: 72699971 https://doi.org/10.3390/biom13030459 |
| dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
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openAccess |
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application/pdf |
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reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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