In vivo antitumor activity by dual stromal and tumor-targeted oncolytic measles viruses

Yuqi Jing, Valery Chavez, Natasha Khatwani, Yuguang Ban, Andrea P. Espejo, Xi Chen, Jaime R. Merchan

Research output: Contribution to journalArticlepeer-review

10 Scopus citations


The tumor stroma acts as a barrier that limits the efficacy of systemically administered oncolytic viruses (OV). We previously demonstrated that stromal-selective, retargeted oncolytic measles viruses (MVs) delay in vivo tumor progression. To further characterize the contribution of stromal targeting to MV’s overall in vivo efficacy in an experimental cancer model, a dual targeted oncolytic measles virus (MV-CD46-muPA) able to simultaneously infect murine stromal (via murine uPAR) and human cancer (via CD46) cells was developed. MV-CD46-muPA infected, replicated, and induced cytotoxicity in both murine and human cancer cells. Viral infection was successfully transferred from stromal to tumor cells in vitro, leading to tumor cell oncolysis. Systemic administration of MV-CD46-muPA led to improved antitumor effects in colon (HT-29) cancer xenografts compared to vehicle or CD46 only targeted MVs. These effects were associated with improved tumor viral deposition, increased apoptosis, and decreases in murine stromal endothelial cells and fibroblasts. MV-CD46-muPA modulated cell cycle, survival, proliferation, and metabolic pathways, as determined by functional proteomic analysis of treated tumors. The above findings further validate the concept that dual stromal and tumor cell viral targeting enhances the therapeutic effects of systemically administered OVs and support further preclinical and clinical development of stromal directed virotherapies.

Original languageEnglish (US)
Pages (from-to)910-922
Number of pages13
JournalCancer gene therapy
Issue number12
StatePublished - Dec 2020
Externally publishedYes

Bibliographical note

Funding Information:
Acknowledgements This work was supported by a research grant from the National Cancer Institute (1R01CA149659-01 to J.R.M.), and by the Sylvester Comprehensive Cancer Center (J.R.M.). We acknowledge Oliver Umland, PhD. from the University of Miami/DRI flow cytometry core facility for technical assistance in flow cytometry experiments.

Publisher Copyright:
© 2020, The Author(s), under exclusive licence to Springer Nature America, Inc.


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