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Review
. 2023 Feb 13;15(2):622.
doi: 10.3390/pharmaceutics15020622.

mRNA-Based Therapeutics in Cancer Treatment

Han Sun  1 , Yu Zhang  1 , Ge Wang  2 , Wen Yang  1 , Yingjie Xu  1   3
Affiliations
Review

mRNA-Based Therapeutics in Cancer Treatment

Han Sun et al. Pharmaceutics. .

Abstract

Over the past two decades, significant technological innovations have led to messenger RNA (mRNA) becoming a promising option for developing prophylactic and therapeutic vaccines, protein replacement therapies, and genome engineering. The success of the two COVID-19 mRNA vaccines has sparked new enthusiasm for other medical applications, particularly in cancer treatment. In vitro-transcribed (IVT) mRNAs are structurally designed to resemble naturally occurring mature mRNA. Delivery of IVT mRNA via delivery platforms such as lipid nanoparticles allows host cells to produce many copies of encoded proteins, which can serve as antigens to stimulate immune responses or as additional beneficial proteins for supplements. mRNA-based cancer therapeutics include mRNA cancer vaccines, mRNA encoding cytokines, chimeric antigen receptors, tumor suppressors, and other combination therapies. To better understand the current development and research status of mRNA therapies for cancer treatment, this review focused on the molecular design, delivery systems, and clinical indications of mRNA therapies in cancer.

Keywords: cancer immunotherapy; delivery; mRNA vaccine; messenger RNA; modification.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Structure and design considerations of IVT mRNAs.
Figure 2
Figure 2
The 5′-cap structures of IVT mRNAs. (a) Structure of cap 0, cap 1, cap 2, and ARCA. (b) Chemical modifications of 5′-cap analogs.
Figure 3
Figure 3
Chemical modifications on bases of IVT mRNAs.
Figure 4
Figure 4
Molecular structures of lipids used in three FDA-approved clinical applications.
Figure 5
Figure 5
Structures of lipoplexes, lipid nanoparticles, and polyplexes.
Figure 6
Figure 6
Overview of mRNA-based cancer immunotherapies.
Figure 7
Figure 7
Design for TMGNEO pDNA. Abbreviations: ARGS, antibiotic resistance genes; T7-P, T7 promoter; SP, signal peptide; TMG, tandem of minigenes; MITD, the trafficking domain of major histocompatibility complex class I; GS, glycine/serine linker.
Figure 8
Figure 8
Design for TAA mRNA. Abbreviations: SP, signal peptide; P2 and P16, the tetanus toxoid CD4+ epitopes P2 and P16; MITD, major histocompatibility complex class I; linker, glycine/serine linker.
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