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Updated: May 22, 2026

Production of High-Titer Recombinant Newcastle Disease Virus from Allantoic Fluid
Published on: May 25, 2022
Extracellular matrix constituents interfere with Newcastle disease virus spread in solid tissue and diminish its
Barak Yaacov1, Itay Lazar2, Shay Tayeb1
1Department of Biochemistry, the Chanock Center for Virology, IMRIC, Hadassah Medical Center-Hebrew University, Jerusalem 91120, Israel.
Abstract:
Advanced melanoma cells, characterized by resistance to chemotherapy, have been shown to be highly sensitive to oncolysis by Newcastle disease virus (NDV). In the present study, we investigated the capacity of NDV to specifically infect and spread into solid tissues of human melanoma and lung carcinoma, in vivo and ex vivo. For this purpose a new model of SCID-beige mice implanted with human melanoma was developed. Surprisingly, the replication competent NDV-MTH and the attenuated, single-cycle replication NDV-HUJ strains, demonstrated a similar oncolytic activity in the melanoma-implanted mice. Further, ex vivo analysis, using organ cultures derived from the melanoma tissues indicated a limited spread of the two NDV strains in the tissue. Extracellular matrix (ECM) molecules, notably heparin sulfate and collagen, were found to limit viral spread in the tissue. This observation was validated with yet another solid tumour of human lung carcinoma. Taken together, the results indicate that the ECM acts as a barrier to virus spread within solid tumour tissues and that this restriction must be overcome to achieve effective oncolysis with NDV.
Insights
Newcastle disease virus (NDV) shows oncolytic potential against advanced melanoma. However, extracellular matrix molecules in solid tumors like melanoma and lung carcinoma limit NDV
Area of Science:
- Oncology
- Virology
- Biotechnology
Background:
- Advanced melanoma and lung carcinoma exhibit chemotherapy resistance.
- Newcastle disease virus (NDV) demonstrates oncolytic activity against cancer cells.
- Understanding NDV's efficacy in solid tumors requires investigating its infectivity and spread.
Purpose of the Study:
- To evaluate the capacity of Newcastle disease virus (NDV) to infect and spread within solid human melanoma and lung carcinoma tissues.
- To assess the oncolytic activity of different NDV strains in vivo and ex vivo models.
- To identify potential barriers to viral spread within solid tumors.
Main Methods:
- Development of a SCID-beige mouse model with human melanoma xenografts.
- In vivo and ex vivo analysis of NDV strains (NDV-MTH and NDV-HUJ) in melanoma and lung carcinoma tissues.
- Investigation of extracellular matrix (ECM) components' role in limiting viral dissemination.
Main Results:
- Both replication-competent and attenuated NDV strains showed similar oncolytic activity in melanoma-bearing mice.
- Ex vivo analysis revealed limited spread of NDV within melanoma and lung carcinoma tissues.
- Extracellular matrix molecules, including heparin sulfate and collagen, were identified as barriers restricting viral spread.
Conclusions:
- The extracellular matrix (ECM) in solid tumors acts as a significant barrier to Newcastle disease virus (NDV) spread.
- Overcoming ECM-mediated restriction is crucial for enhancing NDV's oncolytic efficacy in solid tumors.
- Further research should focus on strategies to mitigate ECM barriers for effective viral oncolysis.
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