<p>The sparking interest in oncolytic viruses (OV) faces challenges in clinical translation due to limitations of pre-clinical models and the lack of predictive biomarkers for OV activity. Furthermore, functional assays which could determine permissivity of human tumors to OVs in a straightforward way are still lacking. Here, we present a novel ex vivo permissivity assay to precisely quantify replication of OVs in viable patient-derived tumors. As example, replication of reporter protein-expressing oncolytic VSV-GP variants was tracked via fluorescence, luminescence or qPCR across 133 patient-derived tumor samples (resection fragments/slices, biopsies) spanning more than 20 tumor entities. Based on the results of our comprehensive testing and by employing VSV-GP-NanoLuc-Katushka, we were able to establish a semi-automated permissivity assay with minimal hands-on time, allowing robust and real-time tracking of viral replication in patient-derived tumor samples. Given the urgent demand for innovative cancer treatments, this novel permissivity assay could be applied to select patients with tumors permissive to OV replication and might thus also show an enhanced clinical response.</p><p></p>

错误:搜索内容不能为空,请输入英文关键词
错误:关键词超出字数限制,请精简
高级检索

An ex vivo permissivity assay to assess replication of the oncolytic virus VSV-GP in patient-derived tumor samples

  • Benjamin Schoeps,
  • Stefanie Estermann,
  • Susanne Berchtold,
  • Julia Beil,
  • Can Yurttas,
  • Melissa Mayr,
  • André Volland,
  • Aida Guerrero Tort,
  • Marlies Christina Glatz,
  • Fabian Martin,
  • Irina Smirnow,
  • Nicole Klammsteiner,
  • Linus D. Kloker,
  • Michaela Smolle,
  • Tobias Nolden,
  • Regina Rettenmaier,
  • Rainer Kleemann,
  • Theresa Schwaiger,
  • Monika Petersson,
  • Knut Elbers,
  • Christiane Knobbe-Thomsen,
  • Ulrich M. Lauer,
  • Krishna Das

摘要

The sparking interest in oncolytic viruses (OV) faces challenges in clinical translation due to limitations of pre-clinical models and the lack of predictive biomarkers for OV activity. Furthermore, functional assays which could determine permissivity of human tumors to OVs in a straightforward way are still lacking. Here, we present a novel ex vivo permissivity assay to precisely quantify replication of OVs in viable patient-derived tumors. As example, replication of reporter protein-expressing oncolytic VSV-GP variants was tracked via fluorescence, luminescence or qPCR across 133 patient-derived tumor samples (resection fragments/slices, biopsies) spanning more than 20 tumor entities. Based on the results of our comprehensive testing and by employing VSV-GP-NanoLuc-Katushka, we were able to establish a semi-automated permissivity assay with minimal hands-on time, allowing robust and real-time tracking of viral replication in patient-derived tumor samples. Given the urgent demand for innovative cancer treatments, this novel permissivity assay could be applied to select patients with tumors permissive to OV replication and might thus also show an enhanced clinical response.