Comparison of DNA and mRNA vaccines against cancer

Abstract

Nucleic acid vaccines (NAVs) have recently been tested as a cancer therapy. DNA and mRNA vaccines deliver genetic information encoding tumor antigens (TAs) to the host, which then produces immune responses against cancer cells that express the TAs. Although NAVs are easy, safe, and simple to manufacture, they have not so far been considered viable alternatives to peptide vaccines. Choosing the right TAs, insufficient immunogenicity, and the immunosuppressive nature of cancer are some challenges to this approach. In this review, we discuss approaches that been used to improve the efficiency of anticancer NAVs.

Figure 1.

The production and function of naked DNA and mRNA vaccines. After determining the sequences of suitable tumor antigens (TAs), the required DNA or mRNA backbone is used in both types of vaccine. For DNA vaccines, amplification is performed in a suitable host cell, such as bacteria, and, after transfection of the purified DNA plasmid, transcription and translation are performed in the nucleus and cytoplasm of the host target cell, respectively (right side). For mRNA vaccines, T7 RNA polymerase is commonly used to amplify the mRNA vaccine in vitro, leaving only translation of TAs to be carried out after transfection (left side). The intracellular TA protein can be proteasomally degraded and routed to the endoplasmic reticulum, where antigenic peptide epitopes (square and sphere shapes) are loaded onto major histocompatibility complex (MHC) I and then presented to CD8⁺ T cells. Extracellular TAs can be taken up by endocytosis and loaded onto MHC II for presentation to helper T cells. Antigen-presenting cells (APCs), such as dendritic cells (DCs), can present antigens (endogenous and exogenous) on both MHC I and MHC II. Most other cells present antigens only on MHC I. Abbreviations: ORF, open reading frame; UTR, untranslated region.