CREATION AND CHARACTERIZATION OF A RECOMBINANT MAMMALIAN ORTHOREOVIRUS EXPRESSING HUMAN EPIDERMAL GROWTH FACTOR RECEPTOR 2 PEPTIDES

Abstract

Mammalian orthoreovirus (MRV) is an oncolytic virus that has been tested in over 30 clinical trials. Increased clinical success has been achieved when MRV is used in combination with other onco-immunotherapies. This has led the field to explore the creation of recombinant MRVs which incorporate immunotherapeutic sequences into the virus genome. This work focuses on creation and characterization of a recombinant MRV, S1/HER2nhd, which expresses three human epidermal growth factor receptor 2 (HER2) peptides (E75, AE36, and GP2) known to induce HER2 specific CD8+ and CD4+ T cells. We show S1/HER2nhd expresses HER2 peptides in infected cells and on the virion, and infects, replicates, and reduces HER2+ breast cancer cell survival. The oncolytic properties of MRV combined with HER2 peptide expression holds potential as a vaccine to prevent recurrences of HER2 expressing cancers.