The ReNAissanCe of mRNA-based cancer therapy

Abstract

About 25 years ago, mRNA became a tool of interest in anticancer vaccination approaches. However, due to its rapid degradation in situ, direct application of mRNA was confronted with considerable skepticism during its early use. Consequently, mRNA was for a long time mainly used for the ex vivo transfection of dendritic cells, professional antigen-presenting cells known to stimulate immunity. The interest in direct application of mRNA experienced a revival, as researchers became aware of the many advantages mRNA offers. Today, mRNA is considered to be an ideal vehicle for the induction of strong immune responses against cancer. The growing numbers of preclinical trials and as a consequence the increasing clinical application of mRNA as an off-the-shelf anticancer vaccine signifies a renaissance for transcript-based antitumor therapy. In this review, we highlight this renaissance using a timeline providing all milestones in the application of mRNA for anticancer vaccination.

Keywords:

• cancer
• dendritic cell
• immunotherapy
• mRNA
• vaccine

Financial & competing interests disclosure

This work was 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 Kanker Liga, an Integrated Project and an EU FP6-funded Network of Excellence, an IWT-TBM program, the FWO-Vlaanderen and the Scientific Fund Willy Gepts of the University hospital Brussels. The use of dendritic cells electroporated with tumor-associated antigen mRNA and TriMix is the topic of a patent WO2009/034172 on which Aude Bonehill and Kris Thielemans are filed as inventors. None of the authors receive any support or remuneration related to this platform. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Key issues

• RNA is a universal molecule and the only one comprising all biochemical functions of life. As such, it remains a central player in all processes involved herein.

• The use of mRNA may offer several advantages in view of anticancer therapy, which makes it a promising off-the-shelf immunotherapeutic and an ideal tool to induce strong immune responses against cancer.

• The production of mRNA can be routinely performed and may therefore meet the rapid developing mRNA field.

• Specific mutations can be adapted to both the mRNA template and the mRNA itself to increase applicability and stability.

• mRNA can be packaged in order to avoid its rapid degradation by ribonucleases, increasing its stability and in addition enhance its delivery to cells.

• Preclinical studies show the potential of mRNA vaccines as an off-the-shelf immunotherapeutic. mRNA vaccines can be used via various routes of delivery.

• mRNA vaccines may become a potent technology platform that can boost cancer specific T cells and induce immunological memory in order to finally avoid both metastatic and recurring cancer cells.

Notes