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Review
. 2022 Jun:107:102405.
doi: 10.1016/j.ctrv.2022.102405. Epub 2022 May 5.

The paradigm shift in treatment from Covid-19 to oncology with mRNA vaccines

Jiao Wei  1 , Ai-Min Hui  2
Affiliations
Review

The paradigm shift in treatment from Covid-19 to oncology with mRNA vaccines

Jiao Wei et al. Cancer Treat Rev. 2022 Jun.

Abstract

mRNA vaccines have gained popularity over the last decade as a versatile tool for developing novel therapeutics. The recent success of coronavirus disease (COVID-19) mRNA vaccine has unlocked the potential of mRNA technology as a powerful therapeutic platform. In this review, we apprise the literature on the various types of cancer vaccines, the novel platforms available for delivery of the vaccines, the recent progress in the RNA-based therapies and the evolving role of mRNA vaccines for various cancer indications, along with a future strategy to treat the patients. Literature reveals that despite multifaceted challenges in the development of mRNA vaccines, the promising and durable efficacy of the RNA in pre-clinical and clinical studies deserves consideration. The introduction of mRNA-transfected DC vaccine is an approach that has gained interest for cancer vaccine development due to its ability to circumvent the necessity of DC isolation, ex vivo cultivation and re-infusion. The selection of appropriate antigen of interest remains one of the major challenges for cancer vaccine development. The rapid development and large-scale production of mRNA platform has enabled for the development of both personalized vaccines (mRNA 4157, mRNA 4650 and RO7198457) and tetravalent vaccines (BNT111 and mRNA-5671). In addition, mRNA vaccines combined with checkpoint modulators and other novel medications that reverse immunosuppression show promise, however further research is needed to discover which combinations are most successful and the best dosing schedule for each component. Each delivery route (intradermal, subcutaneous, intra tumoral, intranodal, intranasal, intravenous) has its own set of challenges to overcome, and these challenges will decide the best delivery method. In other words, while developing a vaccine design, the underlying motivation should be a reasonable combination of delivery route and format. Exploring various administration routes and delivery route systems has boosted the development of mRNA vaccines.

Keywords: Cancer vaccine; Covid-19; Oncology; Optimization; mRNA.

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Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Fig. 1
Fig. 1
The commonly available platforms and mechanisms for cancer vaccine development. (a) Whole cell-based vaccines (an autologous tumor cell vaccine using a patient’s own cancer cells is injected as vaccine). (b) Viral vector-based vaccines (the genome of viral particles is modified to contain one or more genes encoding for the antigens of interest). (c) Dendritic cell-based vaccines (the dendritic cells efficiently capture the antigens, internalize, and process into peptides that are then presented in the context of MHC I and II molecules. These complexes are later recognized by the T-cell receptor (TCR) of CD8+ and CD4 + T cells) (d) DNA based vaccines (DNA plasmids are designed to deliver genes encoding TAs, eliciting or augmenting the adaptive immune response towards TA-bearing tumor cells. It induces the innate immune response, stimulates several DNA-sensing pathways in the cytosol of transfected cells due to the presence of CpG motifs and the double stranded structure itself) (e) Peptide-based vaccines (the peptides bind with the restricted MHC molecule expressed in APC. The peptide/MHC complex is then transported to the cell surface after intracellular processing and later recognized by the TCR on the surface of T cells, leading to activation of T lymphocytes) (f) RNA based vaccines (conventional non-replicating mRNA consists of 5 structural elements such as cap structures, a 5′ untranslated region (5′-UTR), an open reading frame encoding antigens of interest, a 3′-UTR; and an adenine repeating nucleotide sequence that forms a polyadenine (poly(A) tail. The non-replicating mRNA encodes antigen of interest, while self-amplifying mRNA encodes antigen of interest and a replication machinery, a self-replicating single-stranded RNA virus).
Fig. 2
Fig. 2
Mechanism of action of mRNA vaccines. 1. In a cell-free system, mRNA is in vitro transcribed (IVT) from a DNA template. 2. IVT mRNA is then transfected into dendritic cells (DCs) by the process of (3) endocytosis. 4. Endosomal escape allows entrapped mRNA to be released into the cytoplasm. 5. The mRNA is translated into antigenic proteins using the ribosome translational mechanism. After post-translational modification, the translated antigenic protein is ready to act in the cell where it was produced. 6. The protein gets secreted by the host cell. 7. Antigen proteins are digested in the cytoplasm by the proteasome and transferred to the endoplasmic reticulum, where they are loaded onto MHC class I molecules (MHC I). 8. MHC I-peptide epitope complexes with loaded MHC I-peptide epitopes produced, resulting in induction. 9. Exogenous proteins are taken up DCs. 10. They are degraded in endosomes and delivered via the MHC II pathway. Furthermore, to obtain cognate T-cell help in antigen-presenting cells, the protein should be routed through the MHC II pathway. 11. The generated antigenic peptide epitopes are subsequently loaded onto MHC II molecules.
Fig. 3
Fig. 3
Key elements that affect mRNA vaccine stability and translation efficacy. LNP – lipid nanoparticles, RNA – ribonucleic acid, UTR – untranslated region.
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