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Review
. 2021 Feb 25;20(1):41.
doi: 10.1186/s12943-021-01335-5.

mRNA vaccine for cancer immunotherapy

Lei Miao  1 , Yu Zhang  1 , Leaf Huang  2
Affiliations
Review

mRNA vaccine for cancer immunotherapy

Lei Miao et al. Mol Cancer. .

Abstract

mRNA vaccines have become a promising platform for cancer immunotherapy. During vaccination, naked or vehicle loaded mRNA vaccines efficiently express tumor antigens in antigen-presenting cells (APCs), facilitate APC activation and innate/adaptive immune stimulation. mRNA cancer vaccine precedes other conventional vaccine platforms due to high potency, safe administration, rapid development potentials, and cost-effective manufacturing. However, mRNA vaccine applications have been limited by instability, innate immunogenicity, and inefficient in vivo delivery. Appropriate mRNA structure modifications (i.e., codon optimizations, nucleotide modifications, self-amplifying mRNAs, etc.) and formulation methods (i.e., lipid nanoparticles (LNPs), polymers, peptides, etc.) have been investigated to overcome these issues. Tuning the administration routes and co-delivery of multiple mRNA vaccines with other immunotherapeutic agents (e.g., checkpoint inhibitors) have further boosted the host anti-tumor immunity and increased the likelihood of tumor cell eradication. With the recent U.S. Food and Drug Administration (FDA) approvals of LNP-loaded mRNA vaccines for the prevention of COVID-19 and the promising therapeutic outcomes of mRNA cancer vaccines achieved in several clinical trials against multiple aggressive solid tumors, we envision the rapid advancing of mRNA vaccines for cancer immunotherapy in the near future. This review provides a detailed overview of the recent progress and existing challenges of mRNA cancer vaccines and future considerations of applying mRNA vaccine for cancer immunotherapies.

Keywords: Cancer immunotherapy; Cancer vaccine; Ionizable lipids; Lipid nanoparticles (LNPs); Personalized vaccine; Self-amplifying mRNA (SAM); mRNA delivery.

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Conflict of interest statement

LH is a consultant for PDS Biotechnology, Samyang Biopharmaceuticals, and Stemirna Therapeutics. LM is currently a full time employee of Gilead and this article is not related to the underlying work at Gilead and it is with the approval of Gilead. No potential conflict of interest exists.

Figures

Fig. 1
Fig. 1
Representative LNP structure and ionizable lipids used in preclinical research and clinical trials
See this image and copyright information in PMC

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