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| http://dx.doi.org/10.3389/fonc.2017.00271 | DOI Listing |
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Viral products keep gaining importance in multiple therapeutic fields. Considering the scale and production slot limitations, optimizing the outcome of every manufacturing batch is essential to minimize costs and make this therapeutic modality broadly available to patients. Most manufacturing processes for oncolytic viruses currently in clinical studies are based on a batch process.
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Oncolytic vaccinia virus (VVs) based immunotherapy is a rapidly developing treatment for gastrointestinal (GI) cancers. Conventional treatments, such as chemotherapy, radiotherapy and surgery achieve good effects in early-stage GI cancers, but effects are limited in advanced disease. Immunotherapy has limited efficacy in GI cancers due to tumor heterogeneity and complex immunosuppressive mechanisms.
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We previously reported that the DNA alkylator and transcriptional-blocking chemotherapeutic agent trabectedin enhances oncolytic herpes simplex viroimmunotherapy in human sarcoma xenograft models, though the mechanism remained to be elucidated. Here we report trabectedin disrupts the intrinsic cellular antiviral response which increases viral transcript presence in the human tumor cells. We also extended our synergy findings to syngeneic murine sarcoma models, which are poorly susceptible to virus infection.
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