Treatment with mRNA coding for the necroptosis mediator MLKL induces antitumor immunity directed against neo-epitopes

• DOI: 10.1038/s41467-018-05979-8
• Publication Date: 2018-08-20T11:22:33Z
• Authors: Lien Van Hoecke; Sandra Van Lint; Kenny Roose; Alexander Van Parys; Peter Vandenabeele; Johan Grooten; Jan Tavernier; Stefaan De Koker; Xavier Saelens
• Keywords: Immunogenic cell death; Cancer Immunotherapy; Immune checkpoint

Cancer immunotherapy can induce durable antitumor responses. However, many patients poorly respond to such therapies. Here we describe a generic therapy that is based on the intratumor delivery of mRNA codes for necroptosis executioner mixed lineage kinase domain-like (MLKL) protein. This intervention stalls primary tumor growth and protects against distal disseminated formation in syngeneic mouse melanoma colon carcinoma models. Moreover, MLKL-mRNA treatment combined with immune checkpoint blockade further improves activity. rapidly induces T cell responses directed neo-antigens requires CD4+ CD8+ cells prevent growth. Type I interferon signaling Batf3-dependent dendritic are essential this elicit antigen-specific blunts human lymphoma mice reconstituted adaptive system. MLKL-based thus be exploited as an effective immunotherapy.