Bocsan, Andrada Miriam (2026) Influence of Prior Chemotherapy on Oncolytic Virotherapy Efficacy in Neuroblastoma. Master's Research Project 2, Biomedical Sciences.
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Abstract
Neuroblastoma (NB) is a challenging malignancy, particularly in treatment-resistant disease. Oncolytic virotherapy is an emerging therapeutic strategy to overcome NB resistance; however, the effects of prior chemotherapy on viral susceptibility remain poorly understood. We investigated chemotherapy-induced molecular changes affecting oncolytic viruses (OVs) responsiveness using computational and experimental approaches. Our in silico analysis revealed that chemotherapy- and virus-resistant cell lines displayed enhanced innate immune signalling, including interferon and STING pathways, showing reduced viral susceptibility. In contrast, chemotherapy-resistant, viral-sensitive cells showed enrichment in pathways associated with viral replication and RNA synthesis, consistent with viral permisiveness. To validate these findings, NB SK-N-SH cells were treated with Temozolomide, Doxorubicin, or Cisplatin before infection with recombinant Semliki Forest Virus (rSFV). rSFV, an oncolytic alphavirus, has shown strong immunotherapeutic potential for cancer targeting due to its intrinsic tumour-selective replication and immunostimulatory properties. Prior chemotherapy exposure significantly enhanced rSFV infection efficacy and increased CD40+ tumour cell expression. Co-culture of infected SK-N-SH cells with PRAME-specific TCR T cells increased the number of CD69/CD107a-positive CD8+ T cells, indicating enhanced activation and anti-tumour activity. qPCR analysis showed chemotherapy-dependant modulation of antiviral gene expression, with Doxorubicin upregulation of IDO1 and TLR3, while Temozolomide and Cisplatin increased IFN-β and reduced VIPERIN, RIG-1, and TLR3 expression. These findings suggest prior chemotherapy shapes OVs' responsiveness.
| Item Type: | Thesis (Master's Research Project 2) |
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| Supervisor name: | Baarle, D. van |
| Degree programme: | Biomedical Sciences |
| Thesis type: | Master's Research Project 2 |
| Language: | English |
| Date Deposited: | 21 Jul 2026 07:25 |
| Last Modified: | 21 Jul 2026 07:25 |
| URI: | https://fse.studenttheses.ub.rug.nl/id/eprint/37455 |
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