Development of an antitumor vaccine approach based on the delivery of messenger RNA
SEBANE M. 1, FOURNEL S. 1, KICHLER A. 1
1 Université de Strasbourg, Strasbourg, France
Despite the current success of immune checkpoint inhibitors in cancer therapy, broad immunotherapy can result in severe adverse effects such as autoimmunity, highlighting the need for new therapies. In the last decades, therapeutic cancer vaccines have proven to be able to induce strong immune responses with little-to-non adverse effects. Capable of eliciting exceptionally strong immune responses, RNA has emerged as an attractive vaccine platform for cancer therapy. Thus, we propose to develop innovative mRNA-based vaccine formulations that will allow the establishment of an effective anti-tumor immune response.
Current mRNA vaccines are based on cationic lipid formulations which have been shown to induce anti-formulation immunity, impairing the use of the same nanoparticles for future vaccines. Thus, developing suitable next-generation mRNA-based nanoparticles for vaccination is a major challenge.
As a part of our work, we designed cell penetrating peptides (CPPs) derived from viral fusogenic peptides. We investigated the ability of those CPPs to efficiently transfect mRNA into antigen presenting cells (APCs) which are the initiators of the immune response. By using mRNA coding for the reporter gene green fluorescent protein (GFP), we observe a strong transfection efficiency of various APCs (murine macrophages RAW264.7 and dendritic cells DC2.4); and low cytotoxicity;.
We confirmed the ability of our formulations to induce the activation of APCs by analyzing the overexpression of activation markers as well as their ability to induce the presentation of the mRNA encoded antigen (i.e. ovalbumin). Transfected DCs were thus able to induce the activation of effector immune cells by co-culture with T-cells.
Henceforward, we aim to ensure the ability of our formulations to induce immune reactions in vivo. Our molecules could thus represent and easy-to-formulate platform for mRNA vaccination that could be very interesting for cancer therapy.