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Newcastle Disease Virus Virotherapy: Unveiling Oncolytic Efficacy and Immunomodulation
Kawther A Zaher1,2, Jehan S Alrahimi3, Fatemah S Basingab3
1Immunology Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
Abstract:
In virotherapy, cancer cells are eradicated via viral infection, replication, and dissemination (oncolysis).
Background:
This study aims to evaluate the oncolytic potential of Newcastle disease virus (NDV) against colon cancer and explore the immune response associated with its therapeutic effects.
Methods:
NDV was tested for its oncolytic potential in colon cancer cell lines using MTT assays and apoptosis assessments. Tumor-induced mice were treated with NDV, tumor cell lysate (TCL), or a combination of both. After the euthanasia of murine subjects, an assessment of oncolytic efficacy was performed through flow cytometry analysis of murine blood and tumor tissue, targeting CD83, CD86, CD8, and CD4. An ELISA was also performed to examine interferon-gamma levels, interleukin-4 levels, interleukin-12 levels, and interleukin-10 levels in serum and spleen homogenate.
Results:
Cell viability was low in HCT116 and HT-29, indicating a cytotoxic effect in the MTT assay. NDV+TCL recorded the highest rate of cell death (56.72%). NDV+TCL had accelerated cell death after 48 h, reaching 58.4%. The flow cytometry analysis of the blood and tumor of mice with induced tumor treated with combined treatment revealed elevated levels of CD83, CD86, CD8, and CD4 (76.3, 66.9, 83.7, and 14.4%, respectively). The ELISA levels of IFN-γ, IL-4, and IL-12 in serum and the spleen homogenate were elevated (107.6 ± 9.25 pg/mL). In contrast, the expression of IL-10 was significantly reduced (1 ± 0.79).
Insights
Newcastle disease virus (NDV) shows oncolytic potential against colon cancer, enhancing immune responses. Combined NDV and tumor cell lysate (TCL) treatment significantly reduced tumor cell viability and boosted cytotoxic T-cell markers.
Area of Science:
- Oncology
- Virology
- Immunology
Background:
- Virotherapy utilizes viruses for cancer treatment through oncolysis.
- Newcastle disease virus (NDV) is explored for its oncolytic capabilities.
- Investigating NDV's efficacy against colon cancer and its immunomodulatory effects.
Purpose of the Study:
- To evaluate the oncolytic potential of NDV against colon cancer.
- To analyze the immune response elicited by NDV treatment in a colon cancer model.
Main Methods:
- NDV's oncolytic activity was assessed in colon cancer cell lines (HCT116, HT-29) via MTT assays and apoptosis analysis.
- Murine models of colon cancer were treated with NDV, tumor cell lysate (TCL), or a combination (NDV+TCL).
- Immune cell markers (CD83, CD86, CD8, CD4) and cytokine levels (IFN-γ, IL-4, IL-12, IL-10) were quantified using flow cytometry and ELISA.
Main Results:
- NDV demonstrated significant cytotoxic effects on colon cancer cell lines.
- The combination of NDV+TCL resulted in the highest cell death rate (58.4% at 48h).
- NDV+TCL treatment elevated key immune cell markers and pro-inflammatory cytokines (IFN-γ, IL-4, IL-12) while reducing IL-10.
Conclusions:
- NDV exhibits promising oncolytic activity against colon cancer.
- Combination therapy with NDV and TCL enhances anti-tumor immune responses.
- NDV-based virotherapy represents a potential strategy for colon cancer treatment.
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