Intratumoral delivery of mRNA: Overcoming obstacles for effective immunotherapy

Abstract

The immunosuppressive tumor microenvironment (TME) is a major obstacle in cancer immunotherapy. Therefore, it has gained attention as a target site. mRNA emerged as a versatile drug class for cancer therapy. We reported that intratumoral administration of mRNA encoding the fusokine Fβ² supports tumor-specific T-cell immunity. This study provides proof of concept of the use of mRNA to modulate the TME.

Keywords:

• cancer
• CD8⁺ T cell
• dendritic cell
• fusokine
• immunotherapy
• intratumoral
• IFNβ
• mRNA
• TGFβ
• receptor II

Abbreviations:

• CTLs, cytotoxic T lymphocytes
• DCs, dendritic cells
• Fβ², a fusokine consisting of IFNβ, fused to the ectodomain of the TGFβ receptor II
• IMP, investigational medicinal product
• MDSCs, myeloid-derived suppressor cells
• TAAs, tumor-associated antigens
• TiDCs, tumor-infiltrating DCs
• TME, tumor microenvironment

Disclosure of Potential Conflicts of Interest

No potential conflicts of interest were declared.

Funding

The Laboratory of Molecular and Cellular Therapy is supported by grants from the Interuniversity Attraction Poles Program-Belgian State-Belgian Science Policy, the National Cancer Plan of the Federal Ministry of Health, the Stichting tegen Kanker, the Vlaamse Liga tegen Kanker, the FWO-Vlaanderen, the Scientific Fund Willy Gepts of the University Hospital Brussels, SRP research funding of the Vrije Universiteit Brussel, an IWT-TBM program, and an Integrated Project and EU FP7-funded Network of Excellence. Kevin Van der Jeught is a doctoral fellow of the IWT.