Creation and characterization of a recombinant mammalian orthoreovirus expressing σ1 fusion proteins encoding human...

Area of Science:

• Oncology
• Virology
• Immunotherapy

Background:

• Mammalian orthoreovirus (MRV) is an oncolytic virus with demonstrated clinical efficacy, particularly when combined with immunotherapies.
• Recombinant MRVs are being developed to enhance oncolytic activity by incorporating immunotherapeutic sequences.
• Human epidermal growth factor receptor 2 (HER2) is a target in breast cancer therapy, and specific peptides can induce T cell responses.

Purpose of the Study:

• To create and characterize a recombinant MRV, S1/HER2nhd, encoding a fusion protein with HER2-specific peptides.
• To evaluate the expression of the HER2-peptide-containing fusion protein in infected cells and on virions.
• To assess the oncolytic potential of S1/HER2nhd against HER2-positive breast cancer cells.

Main Methods:

• Construction of a recombinant MRV (S1/HER2nhd) expressing a truncated σ1 protein fused to three HER2 peptides (E75, AE36, GP2).
• Analysis of S1/HER2nhd protein expression in infected cells and on purified virions.
• In vitro studies to evaluate viral infectivity, replication, and cytotoxicity in HER2-positive breast cancer cell lines.

Main Results:

• S1/HER2nhd successfully expressed the σ1 fusion protein containing HER2 peptides.
• The fusion protein was detected in infected cells and on the surface of the virions.
• S1/HER2nhd demonstrated infectivity, replication, and significant reduction in survival of HER2-positive breast cancer cells.

Conclusions:

• The engineered oncolytic virus S1/HER2nhd effectively expresses HER2 peptides and exhibits oncolytic activity against HER2-positive cancer cells.
• This recombinant MRV holds promise as a potential vaccine strategy to prevent recurrence in HER2-expressing cancers.