In vivo estimation of oncolytic virus populations within tumors

Mi Yeon Jung, Chetan P. Offord, Matthew K. Ennis, Iris Kemler, Claudia Neuhauser, David M Dingli

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

The use of replication-competent viruses as oncolytic agents is rapidly expanding, with several oncolytic viruses approved for cancer therapy. As responses to therapy are highly variable, understanding the dynamics of therapy is critical for optimal application of virotherapy in practice. Although mathematical models have been developed to understand the dynamics of tumor virotherapy, a scarcity of in vivo data has made difficult parametrization of these models. To tackle this problem, we studied the in vitro and in vivo spread of two oncolytic measles viruses that induce expression of the sodium iodide symporter (NIS) in cells. NIS expression enabled infected cells to concentrate radioactive isotopes that could be reproducibly and quantitatively imaged using SPECT/CT. We observed a strong linear relationship in vitro between infectious virus particles, viral N and NIS gene expression, and radioactive isotope uptake. In vivo radioisotope uptake was highly correlated with viral N and NIS gene expression. Similar expression patterns between viral N and NIS gene expression in vitro and in vivo implied that the oncolytic virus behaved similarly in both scenarios. Significant titers of viable virus were consistently isolated from tumors explanted from mice that had been injected with oncolytic measle viruses. We observed a weaker but positive in vivo relationship between radioisotope uptake and the viable virus titer recovered from tumors; this was likely due to anisotropies in the viral distribution in vivo. These data suggest that methods that enable quantitation of in vivo anisotropies are required for continuing development of oncolytic virotherapy.

Original languageEnglish (US)
Pages (from-to)5992-6000
Number of pages9
JournalCancer Research
Volume78
Issue number20
DOIs
StatePublished - Oct 15 2018

Fingerprint

Oncolytic Viruses
Radioisotopes
Measles virus
Population
Anisotropy
Neoplasms
Viral Load
Gene Expression
Oncolytic Virotherapy
Virus Replication
Virion
Theoretical Models
Therapeutics
In Vitro Techniques

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Jung, M. Y., Offord, C. P., Ennis, M. K., Kemler, I., Neuhauser, C., & Dingli, D. M. (2018). In vivo estimation of oncolytic virus populations within tumors. Cancer Research, 78(20), 5992-6000. https://doi.org/10.1158/0008-5472.CAN-18-0447

In vivo estimation of oncolytic virus populations within tumors. / Jung, Mi Yeon; Offord, Chetan P.; Ennis, Matthew K.; Kemler, Iris; Neuhauser, Claudia; Dingli, David M.

In: Cancer Research, Vol. 78, No. 20, 15.10.2018, p. 5992-6000.

Research output: Contribution to journalArticle

Jung, MY, Offord, CP, Ennis, MK, Kemler, I, Neuhauser, C & Dingli, DM 2018, 'In vivo estimation of oncolytic virus populations within tumors', Cancer Research, vol. 78, no. 20, pp. 5992-6000. https://doi.org/10.1158/0008-5472.CAN-18-0447
Jung, Mi Yeon ; Offord, Chetan P. ; Ennis, Matthew K. ; Kemler, Iris ; Neuhauser, Claudia ; Dingli, David M. / In vivo estimation of oncolytic virus populations within tumors. In: Cancer Research. 2018 ; Vol. 78, No. 20. pp. 5992-6000.
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