Oncolytic Viruses

Oncolytic virotherapy is a promising cancer treatment that uses a replication-competent virus to selectively infect cancer cells, cause cytotoxicity, and generate anti-tumor immunity.  This approach has seen major advances in recent years using both wildtype and genetically engineered viruses.

Analyzing cancer cell killing with high sensitivity and without the need for labels/modifications, the xCELLigence Real-Time Cell Analysis (RTCA) instruments allows the interaction between viruses and target cells to be studied under conditions that approximate human physiology more closely than other in vitro techniques.  By monitoring target cell killing continuously, these instruments also eliminates laborious endpoints measurements and provides cell killing data instantaneously.

Vaccine & Virology Handbook
Download the Vaccine & Virology Handbook to discover a more accurate method to characterize viral activity. Applications include viral titer determination, detection and quantification of neutralizing antibodies, studying anti-viral drugs, testing virucides, oncolytic viruses, and assessing virus quality or fitness.
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The rapid, sensitive, and high throughput xCELLigence Real-Time Cell Analysis Assay is ideal for virus titer determination

Example Data: Quantifying the Potency of Different Oncolytic Viruses

Figure adapted from Molecular Therapy Oncolytics, volume 10(4), Dyer, A. et al. “Oncolytic Group B Adenovirus Enadenotucirev Mediates Non-Apoptotic Cell Death with Membrane Disruption and Release of Inflammatory Mediators,” pages 18–30. This work is licensed under the Creative Commons Attribution 4.0 International License

Killing of A549 lung cancer cells by different adenoviruses. Black arrow indicates the time of virus addition. Virus concentrations are listed as particles per cell (PPC).

In this example xCELLigence RTCA was used to monitor killing of A549 lung cancer cells by a chimeric adenovirus (Enadenotucirev, EnAd). EnAD infects cells by binding to CD46 and/or desmoglein, both widely expressed on many carcinoma cells.  In a potency analysis, the cytotoxicity (i.e. killing kinetics) of EnAd was compared with wild-type adenoviruses Ad11p and Ad5.  At the highest concentration (red, 500 PPC (particles per cells)), EnAd and Ad11p caused complete cell killing (Cell Index decreasing to zero) between 36-48 hours post-infection.  However, at lower virus concentrations (0.8-20 PPC) EnAd was substantially more potent than Ad11p, displayed by both an earlier onset of cytotoxicity and a more rapid completion of cytolysis.  When compared with EnAd and Ad11p, wildtype Ad5 was much less efficient at killing the cancer cells. Ad5 required 5 days to achieve full cell killing even at the highest virus concentration.

This data highlights the ability of xCELLigence RTCA assays to quantitatively capture differences in the potency of different oncolytic viruses.

 

Key Benefits of Using xCELLigence to Monitor Oncolytic Viruses:

  1. Label-Free: Allowing for more physiological assay conditions; labeling or secondary assays aren’t required.
  2. Real-Time: Quantitative monitoring of both fast (hours) and slow (days) killing kinetics.
  3. Sensitive: Capable of evaluating low effector cell to target cell ratios that are physiologically relevant.
  4. Simple Workflow: Requires only the addition of effector cells to target cells (in the presence or absence of antibodies); homogeneous assay without additional sample handling.
  5. Automatic Data Plotting: RTCA software enables facile data display and objective analysis, precluding the subjective data vetting that is common to imaging-based assays.

 

Oncolytic Viruses Publications

 

Featured xCELLigence RTCA Systems for Viral CPE Assays

Dual PurposeSingle PlateMulti PlateHigh Throughput
RTCA DPRTCA SPRTCA MPRTCA HT
3×16 wells1×96 wells6×96 wellsUp to 4×384 wells