Amplifying MRNA Vaccines: Potential Versatile Magicians for Oncotherapy

Overview

Journal Front Immunol

Specialty Allergy & Immunology

Date 2023 Nov 8

PMID 37936701

Authors

Chaoying Hu

Jianyang Liu

Feiran Cheng

Yu Bai

Qunying Mao

Miao Xu

Zhenglun Liang

Affiliations

Soon will be listed here.

Abstract

Cancer vaccines drive the activation and proliferation of tumor-reactive immune cells, thereby eliciting tumor-specific immunity that kills tumor cells. Accordingly, they possess immense potential in cancer treatment. However, such vaccines are also faced with challenges related to their design and considerable differences among individual tumors. The success of messenger RNA (mRNA) vaccines against coronavirus disease 2019 has prompted the application of mRNA vaccine technology platforms to the field of oncotherapy. These platforms include linear, circular, and amplifying mRNA vaccines. In particular, amplifying mRNA vaccines are characterized by high-level and prolonged antigen gene expression at low doses. They can also stimulate specific cellular immunity, making them highly promising in cancer vaccine research. In this review, we summarize the research progress in amplifying mRNA vaccines and provide an outlook of their prospects and future directions in oncotherapy.

Citing Articles

mRNA vaccines in the context of cancer treatment: from concept to application.

Fu Q, Zhao X, Hu J, Jiao Y, Yan Y, Pan X J Transl Med. 2025; 23(1):12.

PMID: 39762875 PMC: 11702060. DOI: 10.1186/s12967-024-06033-6.

mRNA cancer vaccines from bench to bedside: a new era in cancer immunotherapy.

Shariati A, Khani P, Nasri F, Afkhami H, Khezrpour A, Kamrani S Biomark Res. 2024; 12(1):157.

PMID: 39696625 PMC: 11656831. DOI: 10.1186/s40364-024-00692-9.

Advances in mRNA LNP-Based Cancer Vaccines: Mechanisms, Formulation Aspects, Challenges, and Future Directions.

Ramadan E, Ahmed A, Naguib Y J Pers Med. 2024; 14(11).

PMID: 39590584 PMC: 11595619. DOI: 10.3390/jpm14111092.

Progress and prospects of mRNA-based drugs in pre-clinical and clinical applications.

Shi Y, Shi M, Wang Y, You J Signal Transduct Target Ther. 2024; 9(1):322.

PMID: 39543114 PMC: 11564800. DOI: 10.1038/s41392-024-02002-z.

Effect of electrical and chemical (activation versus inactivation) stimulation of the infralimbic division of the medial prefrontal cortex in rats with chronic neuropathic pain.

Moura-Pacheco T, Martins-Pereira R, Medeiros P, Sbragia L, Leite-Panissi C, Machado H Exp Brain Res. 2023; 241(11-12):2591-2604.

PMID: 37725136 DOI: 10.1007/s00221-023-06657-y.

References

Rodriguez-Madoz J, Prieto J, Smerdou C . Semliki forest virus vectors engineered to express higher IL-12 levels induce efficient elimination of murine colon adenocarcinomas. Mol Ther. 2005; 12(1):153-63. DOI: 10.1016/j.ymthe.2005.02.011. View

Weller M, Butowski N, Tran D, Recht L, Lim M, Hirte H . Rindopepimut with temozolomide for patients with newly diagnosed, EGFRvIII-expressing glioblastoma (ACT IV): a randomised, double-blind, international phase 3 trial. Lancet Oncol. 2017; 18(10):1373-1385. DOI: 10.1016/S1470-2045(17)30517-X. View

Zhang H, Zhang L, Lin A, Xu C, Li Z, Liu K . Algorithm for optimized mRNA design improves stability and immunogenicity. Nature. 2023; 621(7978):396-403. PMC: 10499610. DOI: 10.1038/s41586-023-06127-z. View

Sahin U, Oehm P, Derhovanessian E, Jabulowsky R, Vormehr M, Gold M . An RNA vaccine drives immunity in checkpoint-inhibitor-treated melanoma. Nature. 2020; 585(7823):107-112. DOI: 10.1038/s41586-020-2537-9. View

Deng Z, Yang H, Tian Y, Liu Z, Sun F, Yang P . An OX40L mRNA vaccine inhibits the growth of hepatocellular carcinoma. Front Oncol. 2022; 12:975408. PMC: 9606466. DOI: 10.3389/fonc.2022.975408. View

Blakney A, McKay P, Shattock R . Structural Components for Amplification of Positive and Negative Strand VEEV Splitzicons. Front Mol Biosci. 2018; 5:71. PMC: 6070733. DOI: 10.3389/fmolb.2018.00071. View

Crosby E, Hobeika A, Niedzwiecki D, Rushing C, Hsu D, Berglund P . Long-term survival of patients with stage III colon cancer treated with VRP-CEA(6D), an alphavirus vector that increases the CD8+ effector memory T cell to Treg ratio. J Immunother Cancer. 2020; 8(2). PMC: 7661359. DOI: 10.1136/jitc-2020-001662. View

Lapenta C, Gabriele L, Santini S . IFN-Alpha-Mediated Differentiation of Dendritic Cells for Cancer Immunotherapy: Advances and Perspectives. Vaccines (Basel). 2020; 8(4). PMC: 7711454. DOI: 10.3390/vaccines8040617. View

Pal A, Kundu R . Human Papillomavirus E6 and E7: The Cervical Cancer Hallmarks and Targets for Therapy. Front Microbiol. 2020; 10:3116. PMC: 6985034. DOI: 10.3389/fmicb.2019.03116. View

10.

Miles D, Roche H, Martin M, Perren T, Cameron D, Glaspy J . Phase III multicenter clinical trial of the sialyl-TN (STn)-keyhole limpet hemocyanin (KLH) vaccine for metastatic breast cancer. Oncologist. 2011; 16(8):1092-100. PMC: 3228158. DOI: 10.1634/theoncologist.2010-0307. View

11.

Liu D, An C, Bai Y, Li K, Liu J, Wang Q . A Novel Single-Stranded RNA-Based Adjuvant Improves the Immunogenicity of the SARS-CoV-2 Recombinant Protein Vaccine. Viruses. 2022; 14(9). PMC: 9504790. DOI: 10.3390/v14091854. View

12.

Xiong C, Levis R, Shen P, Schlesinger S, Rice C, Huang H . Sindbis virus: an efficient, broad host range vector for gene expression in animal cells. Science. 1989; 243(4895):1188-91. DOI: 10.1126/science.2922607. View

13.

Ballesteros-Briones M, Silva-Pilipich N, Herrador-Canete G, Vanrell L, Smerdou C . A new generation of vaccines based on alphavirus self-amplifying RNA. Curr Opin Virol. 2020; 44:145-153. PMC: 7474593. DOI: 10.1016/j.coviro.2020.08.003. View

14.

Lyons J, Sheahan B, Galbraith S, Mehra R, Atkins G, Fleeton M . Inhibition of angiogenesis by a Semliki Forest virus vector expressing VEGFR-2 reduces tumour growth and metastasis in mice. Gene Ther. 2006; 14(6):503-13. DOI: 10.1038/sj.gt.3302889. View

15.

Sun Q, Zhao X, Peng C, Hao Y, Zhao Y, Jiang N . Immunotherapy for Lewis lung carcinoma utilizing dendritic cells infected with CK19 gene recombinant adenoviral vectors. Oncol Rep. 2015; 34(5):2289-95. PMC: 4583529. DOI: 10.3892/or.2015.4231. View

16.

Oniki S, Nagai H, Horikawa T, Furukawa J, Belladonna M, Yoshimoto T . Interleukin-23 and interleukin-27 exert quite different antitumor and vaccine effects on poorly immunogenic melanoma. Cancer Res. 2006; 66(12):6395-404. DOI: 10.1158/0008-5472.CAN-05-4087. View

17.

Das P, Merits A, Lulla A . Functional cross-talk between distant domains of chikungunya virus non-structural protein 2 is decisive for its RNA-modulating activity. J Biol Chem. 2014; 289(9):5635-53. PMC: 3937639. DOI: 10.1074/jbc.M113.503433. View

18.

Salomon N, Vascotto F, Selmi A, Vormehr M, Quinkhardt J, Bukur T . A liposomal RNA vaccine inducing neoantigen-specific CD4 T cells augments the antitumor activity of local radiotherapy in mice. Oncoimmunology. 2020; 9(1):1771925. PMC: 7458669. DOI: 10.1080/2162402X.2020.1771925. View

19.

Colter J, BIRD H, BROWN R . Infectivity of ribonucleic acid from Ehrlich ascites tumour cells infected with Mengo encephalitis. Nature. 1957; 179(4565):859-60. DOI: 10.1038/179859a0. View

20.

Daemen T, Riezebos-Brilman A, Bungener L, Regts J, Dontje B, Wilschut J . Eradication of established HPV16-transformed tumours after immunisation with recombinant Semliki Forest virus expressing a fusion protein of E6 and E7. Vaccine. 2003; 21(11-12):1082-8. DOI: 10.1016/s0264-410x(02)00558-3. View