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.
Background:
Acute promyelocytic leukaemia (APL) is a clonal disease arising by hematopoietic stem cell (HSC), which characterized by inappropriate proliferation/differentiation or survival of immature myeloid progenitors. Oncolytic adenoviruses have been under widespread investigation as anticancer agents. Recently, our data suggested that tumor cells were cured by AdCN205-IL-24, an adenovirus serotype 5-based conditionally replicating adenovirus expressing IL-24 after infection.
Methods:
In this study, we created a novel fiber chimeric oncolytic adenovirus AdCN306-IL-24 that has Ad11 tropism and approved CAR (coxsackie adenovirus receptor, CAR)-independent cell entry, which could allow development of selective cytopathic effects (CPE) in APL cells in vitro.
Results:
Formidable cytotoxic effect was specifically implemented in APL cells after infection with AdCN306-IL-24. The expression of IL-24 was up-regulated upon treated with accepted tumors. And the vector also induced superior cytolytic effects activity in APL cells by activation of programmed cell death.
Conclusions:
Taken together, our data suggested that chimeric oncolytic adenovirus AdCN306-IL-24 could express
IL-24
gene, representing a potential therapeutics for acute promyelocytic leukemia.
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