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Objective: We evaluate the immunotherapeutic potential of the yellow fever virus vaccine strain 17D (YFV 17D) for intratumoral therapy of pancreatic cancer in mice. Methods: The cytopathic effect of YFV 17D on mouse syngeneic pancreatic cancers cells were studied both in vitro and in vivo and on human pancreatic cancers cells in vitro. Results: YFV 17D demonstrated a strong cytopathic effect against human cancer cells in vitro. Although YFV 17D did not exhibit a lytic effect against Pan02 mouse cells in vitro, a single intratumoral administration of 17D caused a delay in tumor growth and an increase in median survival by 30%. Multiple injections of 17D did not further improve the effect on tumor growth; however, it notably extended the median survival. Furthermore, preliminary immunization with 17D enhanced its oncotherapeutic effect. Conclusions: Intratumoral administration of yellow fever virus vaccine strain 17D delayed tumor in a murine model of pancreatic cancer. The fact that YFV 17D in vitro affected human cancer cells much more strongly than mouse cancer cells appears promising. Hence, we anticipate that the in vivo efficacy of YFV-17D-based oncolytic therapy will also be higher against human pancreatic carcinomas compared to its effect on the mouse pancreatic tumor. [ABSTRACT FROM AUTHOR]

Combined viral and photodynamic therapy for oncological diseases has great potential to treat aggressive tumors such as glioblastomas. A conjugate of vesicular stomatitis virus (VSV) with protoporphyrin IX was prepared, and its oncolytic effects were studied and compared to the effects of the individual components. The VSV showed an oncolytic effect on glioblastoma cell lines T98G and LN229 at a virus titer of 105 TCID50/mL. A VSV titer of 104 TCID50/mL was sufficient for neuroblastoma cell death. A study of the effect of VSV in tumor 3D cell modeling found that VSV had a clear viral cytopathic effect on spheroids of T98G and LN229 cells. Conjugation with the porphyrin significantly reduced the viral titer, but when irradiated, lysis of cells was observed. Photodynamic treatment of T98G and LN229 cells and spheroids with protoporphyrin IX as a photosensitizer also had a cytotoxic effect on cells and, to a lesser extent, on the tumoroids, as complete cell death was not achieved for the tumoroids. The combination therapy, which involved sequential photodynamic therapy using protoporphyrin IX as a photosensitizer and treatment with VSV, was shown to significantly enhance efficacy, resulting in complete cell death of both T98G and LN229 cells and tumoroids. The combination treatment allowed for the use of a lower viral titer (103–104 TCID50/mL) and a lower porphyrin concentration (0.5 μg/mL) to achieve a significant cytotoxic effect. As a result, the implementation of this combination therapy would likely lead to fewer side effects from the treatment. This study clearly demonstrated the excellent perspectives of combination therapy for the treatment of highly aggressive tumors such as glioblastomas. [ABSTRACT FROM AUTHOR]