Oncolytic therapy of a recombinant Newcastle disease virus D90 strain for lung cancer

Area of Science:

• Oncology
• Virology
• Biotechnology

Background:

• Lung cancer remains a leading cause of cancer-related mortality globally.
• Oncolytic virotherapy using Newcastle disease virus (NDV) demonstrates safety and efficacy in preclinical and clinical settings.
• The naturally occurring NDV D90 strain exhibits antiproliferative effects on human lung cancer cells (A549).

Purpose of the Study:

• To develop a reverse genetics system for the NDV D90 strain.
• To generate and characterize recombinant NDV expressing enhanced green fluorescent protein (rNDV-GFP).
• To evaluate the therapeutic potential of parental and recombinant NDV strains in lung cancer models.

Main Methods:

• Construction of a reverse genetics system for NDV D90.
• Generation of recombinant NDV (rNDV-GFP) carrying the enhanced green fluorescent protein gene.
• Assessment of viral replication and apoptosis induction in A549 lung cancer cells.
• In vivo efficacy studies using athymic mice bearing lung cancer xenografts, treated with intratumoral injections of NDV D90, rNDV-D90, and rNDV-GFP.

Main Results:

• Recombinant viruses rNDV-D90 and rNDV-GFP maintained similar replication and apoptotic properties as the parental NDV D90 in A549 cells.
• Both parental D90 virus and recombinant viruses demonstrated tumor-selective replication and induced apoptosis in lung cancer cells.
• Intratumoral administration of NDV D90, rNDV-D90, and rNDV-GFP significantly inhibited tumor growth and prevented body weight loss in mice.

Conclusions:

• The established reverse genetics system provides a platform for developing novel oncolytic viruses based on the NDV D90 strain.
• Recombinant NDV strains show potential as effective therapeutic agents for lung cancer treatment.
• Further development of NDV D90-based recombinant viruses could enhance efficacy in tumor therapy.