Oncolytic virotherapy is a promising cancer treatment that uses a replication-competent virus to selectively infect and kill cancer cells. While this approach can employ wild-type viruses, a great deal of research is being done with viruses that are genetically engineered to achieve higher specificity or efficacy. Engineering an oncolytic adenovirus to express a secreted form of a bi-specific T cell engager, in order to recruit cytotoxic T cells to residual cancer cells, is one such example1.
Because they can monitor cancer cell killing continuously and with high sensitivity, the xCELLigence instruments are an extremely efficient tool for quantitatively assessing the efficacy of oncolytic viruses alone or in combination with other treatment modalities.
In the example below, Arthur Dyer and colleagues at University of Oxford used xCELLigence to monitor the killing of A549 lung cancer cells by a chimeric adenovirus (Enadenotucirev, EnAd) which infects cells by binding to CD46 and/or desmoglein, both of which are expressed on diverse carcinomas. In a potency analysis, the cytotoxicity (i.e. killing kinetics) of EnAd at a range of concentrations was compared with wild-type adenoviruses Ad11p and Ad5. At the highest concentration (red, 500 PPC (particles per cell)), both EnAd and Ad11p caused complete cell killing (Cell Index decreasing to zero) between 36 and 48 hours post-infection. However, at lower virus concentrations (0.8-20 PPC) EnAd is substantially more potent than Ad11p, displaying both an earlier onset of cytotoxicity and a more rapid completion of cytolysis. When compared with EnAd and Ad11p, wildtype Ad5 is much less efficient at killing the cancer cells, requiring 5 days to achieve full cell killing even at the highest virus concentration. Collectively, this data highlights the ability of xCELLigence assays to quantitatively capture differences in the potency of different oncolytic viruses.
|The Killing of A549 lung cancer cells by different adenoviruses. Chimeric adenovirus (Enadenotucirev, EnAd) and wildtype adenoviruses Ad11p and Ad5 were evaluated for their cytolytic potency against A549 cancer cells. Black arrow indicates the time of virus addition. Virus concentrations are listed as particles per cell (PPC). Figure adapted from reference 2.|
xCELLigence instruments that are compatible with virology/vaccine applications:
|Dual Purpose||Single Plate||Multi Plate||High Throughput|
|3×16 wells||1×96 wells||6×96 wells||Up to 4×384 wells|
- Oncolytic adenovirus expressing bispecific antibody targets T-cell cytotoxicity in cancer biopsies. EMBO Mol Med. 2017 Aug;9(8):1067-1087.
- Oncolytic Group B Adenovirus Enadenotucirev Mediates Non-apoptotic Cell Death with Membrane Disruption and Release of Inflammatory Mediators. Mol Ther Oncolytics. 2016 Dec 10;4:18-30.
- Oncolytic Adenoviral Delivery of an EGFR-Targeting T-cell Engager Improves Antitumor Efficacy. Cancer Res. 2017 Apr 15;77(8):2052-2063.
- Novel epi-virotherapeutic treatment of pancreatic cancer combining the oral histone deacetylase inhibitor resminostat with oncolytic measles vaccine virus. Int J Oncol. 2016 Nov;49(5):1931-1944.
- Oncolytic effects of parvovirus H-1 in medulloblastoma are associated with repression of master regulators of early neurogenesis. Int J Cancer. 2014 Feb 1;134(3):703-16.
- Generation of an adenovirus-parvovirus chimera with enhanced oncolytic potential. J Virol. 2012 Oct;86(19):10418-31.
- Efficient and selective tumor cell lysis and induction of apoptosis in melanoma cells by a conditional replication-competent CD95L adenovirus. Exp Dermatol. 2010 Aug;19(8):e56-66.