Assessing the Immunogenicity of DNA Scaffolding for Hybrid Molecular Modalities in THP-1 Cells

Abstract

The IL-33/ST2 complex has been implicated to have a critical role in immune responses towards cancerous tumors. While immunotherapies have been quite successful in blood cancers and melanomas, breast cancers and other solid tumors are rarely responsive and the IL-33/ST2 signaling axis has been suspected to elicit pro-tumoral phenomena. To this end we have designed a multivalent inhibitor composed of small inhibitory peptides hybridized to a DNA scaffold with the goal of facilitating immunotherapies in solid tumors. However, intolerable immune related adverse events (irAEs) are a concern regarding the safety of immune manipulation, such as inducing cytokine storms. To evaluate the impacts of this scaffold, stimulated THP-1 cells were challenged with the DNA scaffolding to determine whether it caused immunogenicity through upregulation of TLR-9. Here we assess the potential immunogenicity of a multivalent molecule DNA scaffolding by challenging THP-1 cells with this complex.