Saadeldin, A. | bioRxiv Science

bioRxiv2026

Ependymomas are cancers of the pre-neural crest/roof plate lineage

Distinct molecular variants of the brain cancer ependymoma are distributed along the rostral-caudal extent of the central nervous system (CNS). Historically proposed to arise from ventricular ependyma, recent studies have suggested conflicting cellular origins, including the neural radial glia and the roof plate lineages. Using single-cell transcriptomics, immunohistochemistry, and lineage tracing, we demonstrate that ependymomas across all CNS compartments transcriptionally mirror MSX1+ve pre-neural crest/roof plate (Pre-NC/RP) lineage derivatives. Ependymoma subgroups recapitulate the spatial and molecular diversity of regional Pre-NC/RP populations, while retaining conserved MSX1 expression. Expression of the oncogenic fusion ZFTA-RELA within the murine Pre-NC/RP lineage generated tumors that faithfully resembled human ependymoma. These findings identify a common embryonic cellular origin for ependymomas and reconcile previously conflicting models of tumorigenesis.

developmental biology↗

bioRxiv2022

Goat PRP14 (gPRP14) has xeno-antigenic properties and works as a vaccine in preclinical models of cancer.

We studied the activity of recombinant goat PRP14 (gPRP14), a member of the RID protein family, as a xeno-antigen in preclinical models of cancer. Antisera from rabbits and mice immunized with gPRP14 showed strong reactivity against several tumor cell types, which was absent towards normal cells: the tumor selectivity was related to surface and intra-cellular expression in tumor cells, and to an exclusively intra-cellular localization in normal cells. In vitro, binding to tumor cells was followed by cytotoxicity which could be rescued by the addition of excess soluble antigen. In vivo, an anti-tumor activity of immunization with gPRP14 was observed in murine syngeneic models of breast cancer and melanoma: the anti-tumor response was present when gPRP14 was administered in a preventive setting, and persisted upon repeated challenges with tumor cells in long-term survivor mice. Finally, we showed that both the humoral and T-cell mediated responses are needed for the optimal anti-tumor effect in the murine melanoma model. Thus, we have performed an initial characterization of gPRP14 as a cancer vaccine, which -given the potential wide range of tumor cells positive for the antigen-appears as a promising, novel immunotherapy.

cancer biology↗