Screening and anti-glioma activity of Chiloscyllium plagiosum anti-human IL-13Rα2 single-domain antibody.

ABSTRACT

Glioblastoma is a common and fatal malignant tumour of the central nervous system, with high invasiveness. Conventional treatments for this disease, including comprehensive treatment of surgical resection combined with chemoradiotherapy, are ineffective, with low survival rate and extremely poor prognosis. Targeted therapy is promising in overcoming the difficulties in brain tumour treatment and IL-13Rα2 is a widely watched target. The development of new therapies for glioma, however, is challenged by factors, such as the unique location and immune microenvironment of gliomas. The unique advantages of single-domain antibodies (sdAbs) may provide a novel potential treatment for brain tumours. In this study, Chiloscyllium plagiosum was immunized with recombinant IL-13Rα2 protein to produce sdAb and sdAb sequences were screened by multi-omics. The targeted sdAb genes obtained were efficiently expressed in the Escherichia coli prokaryotic expression system, showing a significant binding capacity to IL-13Rα2 in vitro. The cell proliferation and migration inhibitory effects of recombinant variable domain of the new antigen receptor (VNAR) on glioma cells were detected by CCK-8 and cell scratch assays. The sdAb obtained in this study showed high in vitro activity and favourable cell proliferation inhibitory effect on glioma cells, with potential clinical application value. The present study also provides a new direction and experimental basis for the development of targeted therapies for glioma.