Evaluation of Apoptosis and Cytotoxicity Induction Using a Recombinant Newcastle Disease Virus Expressing Human IFN-γ...

Area of Science:

• Oncolytic virotherapy
• Cancer biology
• Immunotherapy

Background:

• Prostate cancer is a leading cancer in men, with current treatments causing significant side effects.
• There is a critical need for novel, less toxic prostate cancer therapies.
• Oncolytic viruses (OVs), such as recombinant Newcastle disease virus (rNDV), show promise as an alternative treatment.

Purpose of the Study:

• To engineer and evaluate the oncolytic potential of novel fusogenic rNDVs.
• To assess the efficacy of an rNDV expressing human interferon-gamma (IFN-γ) against prostate cancer cells.
• To investigate the virus's ability to reduce cancer cell viability and induce apoptosis.

Main Methods:

• Developed two highly fusogenic rNDVs: rFLCF5nt (parental) and rFLCF5nt-IFN-γ (expressing IFN-γ), using rNDV rLS1 as a backbone.
• Confirmed stable expression and protein integrity of IFN-γ in the engineered virus.
• Evaluated oncolytic activity in DU145 prostate cancer cells using MTS and Annexin V-PE assays.

Main Results:

• The IFN-γ-expressing virus demonstrated stable IFN-γ protein expression after multiple passages.
• Both the parental and IFN-γ-expressing rNDVs exhibited significantly high oncolytic activity against DU145 cells.
• A significant reduction in cell viability and induction of apoptosis were observed compared to the control virus (p < 0.0001).

Conclusions:

• The engineered IFN-γ-expressing virus effectively reduces human prostate cancer cell viability in vitro.
• This virus has the potential to induce apoptosis in prostate cancer cells, supporting its use in virotherapy.
• Further research into this IFN-γ-expressing rNDV could lead to new therapeutic strategies for prostate cancer.