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- W2563850866 abstract "Local recurrence and remote metastasis are major challenges to overcome for improving the survival of cancer patients after surgery. The main source for these is the minimal residual disease (MRD) that remains in situ after resection in microscopic deposits beyond the clearance margins and in micrometastases (lymphatic or haematogenous). There is increasing evidence that surgical intervention can actually promote tumour recurrence and distant metastass by several mechanisms including suppression of NK cells and prominent Th2 polarisation. Tumour-targeted oncolytic viruses (TOVs) are attractive therapeutics for cancer because they selectively amplify through replication and spread the input dose of virus in the target tumour. TOVs not only kill the tumorr cells by direct lysis but also attack them through multiple other mechanisms of action, especially breaking down the immuno-suppressive tumor microenvironment and inducing a long-lasting tumour-specific immunity. In addition, TOVs can specifically deliver therapeutic proteins into tumours at increasing levels following viral replication within the malignant cells. We have recently created a novel tumour-targeted oncolytic vaccinia virus (VVDTKDN1L). Treatment with this virus resulted in strong NK cell activation and potent tumour-specific immunity, and dramatically reduced lung metastasis after surgery in several cancer models when used as a neo-adjuvant therapeutic agent. To improve its anti-tumour efficacy further, we armed VVDTKDN1L with several immunomodulatory genes. Here we demonstrated that VVDTKDN1L-IL12 is the most effective therapeutic agent and resulted in complete eradication of tumours in 86% of mice bearing subcutaneous pancreatic cancer tumours. Strikingly, five daily treatments with the VVDTKDN1L-IL12 before surgery dramatically improved animal survival and even cured most animals whereas the GM-CSF-armed virus did not show benefit compared to the unarmed backbone virus. These data provide proof of concept for translation of the regime into clinical trials. This new approach may significantly improve the survival of cancer patients in the future." @default.
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- W2563850866 date "2015-05-01" @default.
- W2563850866 modified "2023-09-24" @default.
- W2563850866 title "420. A Promising Neo-Adjuvant Immuno-Therapeutic Agent for Preventing Cancer Recurrence and Metastasis After Surgery" @default.
- W2563850866 doi "https://doi.org/10.1016/s1525-0016(16)34029-1" @default.
- W2563850866 hasPublicationYear "2015" @default.
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