Nanobodies targeting ABCC3 for immunotargeted applications in glioblastoma

Ruiz-López, Eduardo (author), Jovchevska, Ivana (author), Schuhmacher, Alberto J. (author)

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.

• Language: English
• Keywords: glioblastoma, nanobodies, immunotargeted applications, antibody fragment therapy, biologics, CNS cancer
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: MF - Faculty of Medicine
• Publication status: Published
• Publication version: Version of Record
• Year: 2022
• Number of pages: 12 str.
• Numbering: Vol. 12, art. 22581
• PID: 20.500.12556/RUL-165165
• UDC: 616-006
• ISSN on article: 2045-2322
• DOI: 10.1038/s41598-022-27161-3
• COBISS.SI-ID: 136531971
• Publication date in RUL: 26.11.2024

Record is a part of a journal

• Title: Scientific reports
• Shortened title: Sci. rep.
• Publisher: Springer Nature
• ISSN: 2045-2322
• COBISS.SI-ID: 18727432

Licences

• License: CC BY 4.0, Creative Commons Attribution 4.0 International
• Link: http://creativecommons.org/licenses/by/4.0/
• Description: This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.

Secondary language

• Language: Slovenian
• Keywords: glioblastom, nanotelesa, imunsko usmerjene aplikacije