Nanobodies targeting ABCC3 for immunotargeted applications in glioblastoma
Abstract The cancer “omics” reveal many clinically relevant alterations that are transforming the molecular characterization of glioblastomas. However, many of these findings are not yet translated into clinical practice due, in part, to the lack of non-invasive biomarkers and the limitations impose...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2022-12-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-27161-3 |
| _version_ | 1797973610322722816 |
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| author | Eduardo Ruiz-López Ivana Jovčevska Ruth González-Gómez Héctor Tejero Fátima Al-Shahrour Serge Muyldermans Alberto J. Schuhmacher |
| author_facet | Eduardo Ruiz-López Ivana Jovčevska Ruth González-Gómez Héctor Tejero Fátima Al-Shahrour Serge Muyldermans Alberto J. Schuhmacher |
| author_sort | Eduardo Ruiz-López |
| collection | DOAJ |
| description | Abstract The cancer “omics” reveal many clinically relevant alterations that are transforming the molecular characterization of glioblastomas. However, many of these findings are not yet translated into clinical practice due, in part, to the lack of non-invasive biomarkers and the limitations imposed by the blood–brain barrier. Nanobodies, camelid single-domain antibody fragments, emerge as a promising tool for immunotargeted applications for diagnosing and treating glioblastomas. Performing agnostic bioinformatic analysis from glioblastoma patient datasets, we identified ATP Binding Cassette subfamily C member 3 (ABCC3) as a suitable target for immunotargeted applications. The expression of ABCC3 is associated with poor survival and impaired response to temozolomide. Importantly, high expression of ABCC3 is restricted to glioblastoma, with negligible levels in healthy brain tissue, and further correlates with tumor grade and stemness markers. We identified three immunogenic epitopes of ABCC3 which were used to isolate nanobodies from a glioblastoma-specific phage-display nanobody library. Two nanobodies targeting ABCC3 (NbA42 and NbA213) were further characterized and demonstrated in vivo selective recognition of ABCC3 in glioblastoma xenograft mouse models upon systemic administration. We designate NbA42 and NbA213 as new candidates to implement immunotargeted applications guiding a more personalized and precise diagnosis, monitoring, and treatment of glioblastoma patients. |
| first_indexed | 2024-04-11T04:07:00Z |
| format | Article |
| id | doaj.art-0affb9e0bbb04e53b8f93d6798240ad8 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-11T04:07:00Z |
| publishDate | 2022-12-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-0affb9e0bbb04e53b8f93d6798240ad82023-01-01T12:18:45ZengNature PortfolioScientific Reports2045-23222022-12-0112111210.1038/s41598-022-27161-3Nanobodies targeting ABCC3 for immunotargeted applications in glioblastomaEduardo Ruiz-López0Ivana Jovčevska1Ruth González-Gómez2Héctor Tejero3Fátima Al-Shahrour4Serge Muyldermans5Alberto J. Schuhmacher6Molecular Oncology Group, Instituto de Investigación Sanitaria Aragón (IIS Aragón)Center for Functional Genomics and Biochips, Institute of Biochemistry and Molecular Genetics, Faculty of Medicine, University of LjubljanaMolecular Oncology Group, Instituto de Investigación Sanitaria Aragón (IIS Aragón)Bioinformatics Unit, Centro Nacional de Investigaciones Oncológicas (CNIO)Bioinformatics Unit, Centro Nacional de Investigaciones Oncológicas (CNIO)Cellular and Molecular Immunology, Vrije Universiteit BrusselMolecular Oncology Group, Instituto de Investigación Sanitaria Aragón (IIS Aragón)Abstract The cancer “omics” reveal many clinically relevant alterations that are transforming the molecular characterization of glioblastomas. However, many of these findings are not yet translated into clinical practice due, in part, to the lack of non-invasive biomarkers and the limitations imposed by the blood–brain barrier. Nanobodies, camelid single-domain antibody fragments, emerge as a promising tool for immunotargeted applications for diagnosing and treating glioblastomas. Performing agnostic bioinformatic analysis from glioblastoma patient datasets, we identified ATP Binding Cassette subfamily C member 3 (ABCC3) as a suitable target for immunotargeted applications. The expression of ABCC3 is associated with poor survival and impaired response to temozolomide. Importantly, high expression of ABCC3 is restricted to glioblastoma, with negligible levels in healthy brain tissue, and further correlates with tumor grade and stemness markers. We identified three immunogenic epitopes of ABCC3 which were used to isolate nanobodies from a glioblastoma-specific phage-display nanobody library. Two nanobodies targeting ABCC3 (NbA42 and NbA213) were further characterized and demonstrated in vivo selective recognition of ABCC3 in glioblastoma xenograft mouse models upon systemic administration. We designate NbA42 and NbA213 as new candidates to implement immunotargeted applications guiding a more personalized and precise diagnosis, monitoring, and treatment of glioblastoma patients.https://doi.org/10.1038/s41598-022-27161-3 |
| spellingShingle | Eduardo Ruiz-López Ivana Jovčevska Ruth González-Gómez Héctor Tejero Fátima Al-Shahrour Serge Muyldermans Alberto J. Schuhmacher Nanobodies targeting ABCC3 for immunotargeted applications in glioblastoma Scientific Reports |
| title | Nanobodies targeting ABCC3 for immunotargeted applications in glioblastoma |
| title_full | Nanobodies targeting ABCC3 for immunotargeted applications in glioblastoma |
| title_fullStr | Nanobodies targeting ABCC3 for immunotargeted applications in glioblastoma |
| title_full_unstemmed | Nanobodies targeting ABCC3 for immunotargeted applications in glioblastoma |
| title_short | Nanobodies targeting ABCC3 for immunotargeted applications in glioblastoma |
| title_sort | nanobodies targeting abcc3 for immunotargeted applications in glioblastoma |
| url | https://doi.org/10.1038/s41598-022-27161-3 |
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