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- W4306756087 abstract "ABSTRACT Medulloblastoma is the most common childhood brain tumor with an unfavorable prognosis and limited options of harmful treatments that are associated with devastating long-term side effects. Therefore, the development of safe, non-invasive and effective therapeutic approaches is required to save the quality of life of young medulloblastoma survivors. We postulated that therapeutic targeting is a solution. Thus, we used a recently designed tumor-targeted bacteriophage (phage)-derived particle, named transmorphic phage/AAV, TPA, to deliver a transgene expressing the tumor necrosis factor alpha ( TNFα ) for targeted systemic therapy of medulloblastoma. This vector was engineered to display the double cyclic RGD4C peptide to selectively target tumors after intravenous administration. Furthermore, the lack of native phage tropism to mammalian cells warrants safe and selective systemic delivery to the tumor microenvironment. In vitro RGD4C.TPA. TNFα treatment of human medulloblastoma cells generated efficient and selective TNFα expression, subsequently triggering cell death. Combination with the chemotherapeutic drug cisplatin, used clinically against medulloblastoma, resulted in augmented effect through the enhancement of TNFα gene expression. Systemic administration of RGD4C.TPA. TNFα to mice bearing subcutaneous medulloblastoma xenografts resulted in selective tumor homing of these particles, and consequently targeted tumor expression of TNFα, apoptosis, and destruction of the tumor vasculature. Thus, our RGD4C.TPA. TNFα particle provides selective and efficient systemic delivery of TNFα to medulloblastoma, yielding a potential TNFα anti-medulloblastoma therapy while sparing healthy tissues from the systemic toxicity of this cytokine." @default.
- W4306756087 created "2022-10-19" @default.
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- W4306756087 date "2022-10-18" @default.
- W4306756087 modified "2023-10-01" @default.
- W4306756087 title "Transmorphic phage-guided systemic delivery of<i>TNFα</i>gene for the treatment of human paediatric medulloblastoma" @default.
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- W4306756087 doi "https://doi.org/10.1101/2022.10.18.512650" @default.
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