Functional targeted therapy has unfortunately failed to improve the outcome of glioblastoma patients. While success stories evidenced by the use of antibody-drug conjugates or ADC in other tumor types are encouraging, targets specific to glioblastoma and accessible through the blood stream remain scarce. In an article published in the Journal of Proteome Research, Andrei Turtoi, Arnaud Blomme, Elettra Bianchi have identified and characterized novel and accessible proteins using an innovative proteomic approach on 6 human glioblastomas.

The corresponding supporting data has been deposited in the PRIDE (PRoteomics IDEntifications) database (ID: PXD001398), a public data repository of mass spectrometry (MS) based proteomics data, which is maintained by European Bioinformatics Institute as part of the Proteomics Services Team.

Among several clusters of uniquely expressed proteins, the authors highlight collagen-VI-alpha-1 (COL6A1) as a highly expressed tumor biomarker with low levels in most normal tissues. However, immunohistochemical analysis of glioma samples from 61 patients demonstrated that COL6A1 is a significant and consistent feature of high-grade glioma. Deposits of COL6A1 were evidenced in the perivascular regions of the tumor-associated vasculature and in glioma cells found in pseudopalisade structures. Retrospective analysis of public gene-expression datasets from over 300 glioma patients emphasized a significant correlation of poor patient outcome and high COL6A1 expression.

In a proof of concept study the authors used chicken chorioallantoic membrane in vivo model to show that COL6A1 is a reachable target for IV injected and fluorescently labeled antibodies. Based on the outcomes of their study, the scientists believe that the present data warrants further development of human COL6A1 antibodies for assessing the quantitative biodistribution in the preclinical tumor models.

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Published in: Journal of Proteome Research