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. 2023 Dec 29;16(1):59.
doi: 10.3390/pharmaceutics16010059.

Sensitizing the Efficiency of ICIs by Neoantigen mRNA Vaccines for HCC Treatment

Rui Han  1   2   3   4 , Yuqian Wang  1   2 , Lingeng Lu  4   5   6
Affiliations

Sensitizing the Efficiency of ICIs by Neoantigen mRNA Vaccines for HCC Treatment

Rui Han et al. Pharmaceutics. .

Abstract

This study builds upon the groundbreaking mRNA vaccine Nobel Prize win in 2023 for COVID-19 prevention, paving the way for next-generation mRNA cancer vaccines to revolutionize immunotherapy. Despite the existing challenges, such as the presence of a suppressive tumor microenvironment and the identification of cancer-associated antigens, recent results from the KEYNOTE-942 trial have successfully demonstrated the effectiveness of mRNA-based cancer treatments, providing clinical evidence for the first time. This trial aimed to evaluate the efficacy and safety of combining immune checkpoint inhibitors with mRNA-based therapies in treating cancer. This advancement undeniably represents new hope for hepatocellular carcinoma (HCC) patients. However, progress in this field remains limited. In this article, we summarized the current state of applying immune checkpoint inhibitors (ICIs) combined with neoantigen mRNA vaccines. Additionally, we discussed potential targets for designing novel mRNA vaccines and potential mRNA vaccine delivery vehicles. The objective of this article is to inspire enthusiasm for the exploration of innovative therapeutic strategies that combine ICIs with neoantigen mRNA vaccines for HCC treatment and HCC prevention.

Keywords: HCC; combined therapy; immune checkpoint inhibitor; neoantigen mRNA vaccines; novel therapeutic strategy.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
The potential advantages of adding neoantigen mRNA vaccine in ICI-based therapy for treating HCC, which are overcoming immune suppression, personalization, and combating resistance.
Figure 2
Figure 2
Milestones of selected mRNA vaccine research and development. At present, two mRNA vaccines are being tested in clinical trials for treating HCC combined with immune checkpoint inhibitors (ICIs). Some potential tumor-specific antigens for novel mRNA vaccine have also been reported by several preclinical studies.
Figure 3
Figure 3
Potential mechanisms of applying neoantigen mRNA vaccine in HCC treatment. Neoantigens are unique mutations in cancer cells that can be targeted by personalized cancer vaccines. Neoantigen mRNA vaccines introduce synthetic mRNA encoding patient-specific neoantigens, which are translated into proteins by APCs. This activates T cells to eliminate cancer cells. Combining neoantigen vaccines with ICIs overcomes immune suppression, personalizes treatment, and combats resistance to ICIs. The combination enhances the immune response and improves outcomes in cancer immunotherapy.
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