Nanobodies targeting ABCC3 for immunotargeted applications in glioblastoma.

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.

Diagnosis of Pancreatic Ductal Adenocarcinoma by Immuno-Positron Emission Tomography.

Diagnosis of pancreatic ductal adenocarcinoma (PDAC) by current imaging techniques is useful and widely used in the clinic but presents several limitations and challenges, especially in small lesions that frequently cause radiological tumors infra-staging, false-positive diagnosis of metastatic tumor recurrence, and common occult micro-metastatic disease. The revolution in cancer multi-"omics" and bioinformatics has uncovered clinically relevant alterations in PDAC that still need to be integrated into patients' clinical management, urging the development of non-invasive imaging techniques against principal biomarkers to assess and incorporate this information into the clinical practice. "Immuno-PET" merges the high target selectivity and specificity of antibodies and engineered fragments toward a given tumor cell surface marker with the high spatial resolution, sensitivity, and quantitative capabilities of positron emission tomography (PET) imaging techniques. In this review, we detail and provide examples of the clinical limitations of current imaging techniques for diagnosing PDAC. Furthermore, we define the different components of immuno-PET and summarize the existing applications of this technique in PDAC. The development of novel immuno-PET methods will make it possible to conduct the non-invasive diagnosis and monitoring of patients over time using in vivo, integrated, quantifiable, 3D, whole body immunohistochemistry working like a "virtual biopsy".