Targeting a Tumor-Specific Epitope on Podocalyxin Increases Survival in Human Tumor Preclinical Models.

Podocalyxin (Podxl) is a CD34-related cell surface sialomucin that is normally highly expressed by adult vascular endothelia and kidney podocytes where it plays a key role in blocking adhesion. Importantly, it is also frequently upregulated on a wide array of human tumors and its expression often correlates with poor prognosis. We previously showed that, in xenograft studies, Podxl plays a key role in metastatic disease by making tumor initiating cells more mobile and invasive. Recently, we developed a novel antibody, PODO447, which shows exquisite specificity for a tumor-restricted glycoform of Podxl but does not react with Podxl expressed by normal adult tissue. Here we utilized an array of glycosylation defective cell lines to further define the PODO447 reactive epitope and reveal it as an O-linked core 1 glycan presented in the context of the Podxl peptide backbone. Further, we show that when coupled to monomethyl auristatin E (MMAE) toxic payload, PODO447 functions as a highly specific and effective antibody drug conjugate (ADC) in killing ovarian, pancreatic, glioblastoma and leukemia cell lines

Informations de copyright

Copyright © 2022 Canals Hernaez, Hughes, Li, Mainero Rocca, Dean, Brassard, Bell, Samudio, Mes-Masson, Narimatsu, Clausen, Blixt, Roskelley and McNagny.

Déclaration de conflit d'intérêts

The authors DC, MH, PD, IS, OB, KM, CR are inventors of a pending patent application on PODO447 and methods of using the same (US20180296673A1). MH, KM and CR are inventors of a pending patent application on PODO83 and methods of using the same (US20190367606A1). KM and CR possess an awarded patent on podocalyxin as a prognostic marker in cancer (US9309323B2). The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.