mRNA vaccine for cancer immunotherapy

Abstract

AbstractmRNA 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.

Editorial: mRNA Vaccines and Immunotherapy in Oncology: A New Era for Personalized Medicine

“…The rationale for developing mRNA-based vaccines for cancer immunotherapy is not to prevent cancer but to destroy tumor cells in the patient [ 1 , 2 ]. Initial preclinical studies on mRNA vaccines were conducted in animal models and showed efficacy that was not supported in clinical studies [ 2 , 3 ]. In the past decade, there have been rapid developments in checkpoint inhibitors, vaccine adjuvants, vaccine delivery systems, and increased understanding of the tumor microenvironment, including the roles of antigen-presenting cells (APCs) [ 4 ].…”

“…Other challenges to mRNA vaccine development included the instability of mRNA and its low immunogenicity, which initially resulted in poor immune responses [ 4 ]. These initial challenges were overcome by mRNA sequence optimization, and current advantages of mRNA vaccines include their safety and efficacy and the ability for manufacturing on a mass scale [ 3 , 4 ],…”

“…There have also been some recent developments in dendritic cell-based mRNA vaccines [ 5 ]. Vaccination with isolated mRNA, or vehicle-loaded mRNA, results in tumor antigen expression by APCs, which leads to activation of the innate and adaptive immune responses [ 1 3 ].…”

Scrutinizing Coronaviruses Using Publicly Available Bioinformatic Tools: The Viral Structural Proteins as a Case Study

“…All four use coding sequences for the spike protein. The latest developments will certainly also contribute to our fight, not only against other types of viral infections, but also against cancer ( Pardi et al, 2018 ; Zhang et al, 2019 ; Xu et al, 2020b ; Miao et al, 2021 ).…”

Assessing immune response upon systemic RNA vaccination on [18F]-FDG PET/CT for COVID-19 vaccine and then for immuno-oncology?

“…The technology of mRNA vaccination offers promising prophylactic and therapeutic potentials in several medical fields including immuno-oncology [4]. Therefore, current oncological clinical trials should consider the potential theranostic value of [18F]-FDG PET and correlate temporal changes in glucose metabolism of lymphoid tissues with treatment outcome.…”