2283P - Assessing the replicative potential of the oncolytic virus VSV-GP in patient-derived tumor biopsies ex vivo

Background

The understanding of human cancers has increased substantially within the past decade. However, translation of the acquired knowledge into clinical success is still remarkably low. This gap between scientific progress and clinical application is decisively driven by limitations of preclinical models, which often do not sufficiently mimic the complex microenvironment and heterogeneity of human tumors. Therefore, assays allowing for enrichment of human tumors responsive to complex immunotherapies, such as oncolytic virotherapy, are urgently needed. Here, we employed a patient-derived tumor biopsy culture system to assess susceptibility of individual human tumor ecosystems to the oncolytic virus VSV-GP ex vivo.

Methods

A simplified ex vivo culture system of patient-derived tumor biopsies was established and compared to the tumor slice culture approach previously set up in our laboratories. Viability and tissue integrity of human colorectal and pancreatic cancer samples were studied by metabolic activity and histopathology, respectively. Susceptibility of biopsies and slice cultures derived from murine tumors, as well as more heterogenous human tumors to the oncolytic virus VSV-GP was assessed. In particular, virus replication kinetics was monitored over time by using reporter protein-tagged VSV-GP variants and fluorescence microscopy in combination with quantification of viral genomes via qRT-PCR.

Results

Patient derived tumor samples retained viability and histological integrity during overnight storage at 4°C, mimicking the transport from the clinics to the lab, as well as during ex vivo cultivation for up to 72h. Biopsies and slice cultures derived from murine tumors showed similar susceptibility to VSV-GP. These results could furthermore be substantiated in more complex patient-tumor derived samples, where VSV-GP propagated to a similar extent in tumor biopsies and tumor slice cultures.

Conclusions

The here-described assay allows simple and straightforward ex vivo analysis of patient-derived tumor biopsies for susceptibility towards oncolytic viruses. This assay may open new avenues towards enrichment of cancer patients responsive to VSV-GP based oncolytic virotherapy.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

ViraTherapeutics GmbH, Medical University of Innsbruck, University Hospital Tübingen, Boehringer Ingelheim Pharma GmbH & Co. KG.

Funding

ViraTherapeutics GmbH, Boehringer Ingelheim Pharma GmbH & Co. KG.

Disclosure

B. Schoeps, M. Mayr, M. Glatz, S. Estermann, A. Guerrero Tort, C. Knobbe-Thomsen, T. Nolden, K. Elbers, M. Petersson: Financial Interests, Personal and Institutional, Full or part-time Employment: ViraTherapeutics. R. Kleemann: Financial Interests, Personal and Institutional, Full or part-time Employment: Boehringer Ingelheim. All other authors have declared no conflicts of interest.