mRNA Cancer Vaccines: Construction and Boosting Strategies

Abstract

In late 2020, the U.S. Food and Drug Administration (FDA) approved a lipid-based mRNA vaccine for the prevention of COVID-19, which has pushed this field to be more closely studied and motivated researchers to delve deeper into mRNA therapeutics. To date, the research on mRNA cancer vaccines has been developed rapidly, and substantial hopeful therapeutic results have been achieved against various solid tumors in clinical trials. In this review, we first introduce three main components of mRNA cancer vaccines, including mRNA antigens, adjuvants, and delivery vectors. Engineering these components can optimize the therapeutic effects of mRNA cancer vaccines. For instance, appropriate modification of mRNA structure can alleviate the poor stability and innate immunogenicity of mRNA, and the use of mRNA delivery vectors can address the issues of low delivery efficiency in vivo. Second, we emphatically discuss some strategies to further improve the efficacy of mRNA cancer vaccines, namely modulating the immunosuppressive tumor environment, optimizing administration routes, achieving targeting delivery to intended tissues or organs, and employing combination therapy. These strategies can strengthen the tumor inhibitory ability of mRNA cancer vaccines and increase the possibility of tumor elimination. Finally, we point out some challenges in the clinical practice of mRNA cancer vaccines and offer our perspectives on future developments in this rapidly evolving field. It is anticipated that mRNA cancer vaccines will be rapidly developed for clinical cancer therapy in the near future.

High-Throughput Screening of Polymer Library for mRNA Tumor Vaccine Carriers with Innate Adjuvant Properties

“…Many studies have shown that moderate immune stimulation is beneficial to improve the effectiveness of the vaccine. − We then employed the P6/mOVA nanovaccine to investigate the influence of the polymeric nanocarrier on DC maturation and activation. According to Figure a, the group with only P6 had a certain effect on promoting the maturation of DC2.4 cells.…”

Adjuvants for cancer mRNA vaccines in the era of nanotechnology: strategies, applications, and future directions

“…mRNA vaccines can encode almost any protein and facilitate post-translational modifications within cells. This capability reduces immunogenicity while ensuring the functionality of protein products, leading to significant breakthroughs in treating various diseases [ 5 – 7 ]. (2) Efficiency .…”

“…According to the traditional view, an mRNA vaccine comprises three components: mRNA sequence containing antigen, DDS or vector, and adjuvant. Adjuvant is an immunostimulant that is added in addition to a vector or DDS to non-specifically enhance the body’s specific immune response to the antigen [ 7 ]. Conversely, some scholars argue that adjuvants should include DDS in addition to traditional adjuvants [ 20 ].…”

The Limitations of Current T Cell-Driven Anticancer Immunotherapies Can Be Overcome with an Original Extracellular-Vesicle-Based Vaccine Strategy

“…Both the reactivation and ex novo generation of T cell-driven antitumor activity are the ultimate goals of several anticancer immunotherapies, including those based on immune checkpoint inhibitors (ICIs) [ 2 ], chimeric antigen receptor (CAR) T cells [ 3 ], and mRNA-based vaccines [ 4 ]. At present, ICIs and CAR-T cells are in use in clinics.…”