Recent developments of RNA-based vaccines in cancer immunotherapy

ABSTRACT

Introduction

Cancer immunotherapy is more dependent on monoclonal antibodies, proteins, and cells, as therapeutic agents, to attain prominent outcomes. However, cancer immunotherapy’s clinical benefits need to be enhanced, as many patients still do not respond well to existing treatments, or their diseases may relapse after temporary control. RNA-based approaches have provided new options for advancing cancer immunotherapy. Moreover, considerable efforts have been made to utilize RNA for vaccine production. RNA vaccines, which encode tumor-associated or specific epitopes, stimulate adaptive immunity. This adaptive immune response is capable of elimination or reduction of tumor burden. It is crucial to develop effective RNA transfer technologies that penetrate the lipid bilayer to reach the cytoplasm for translation into functional proteins. Two important delivery methods include the loading of mRNA into dendritic cells ex vivo; and direct injection of naked RNA with or without a carrier.

Areas covered

The latest results of pre-clinical and clinical studies with RNA vaccines in cancer immunotherapy are summarized in this review.

Expert opinion

RNA vaccines are now in early clinical development with promising safety and efficacy outcomes. Also, the translation capacity and durability of these vaccines can be increased with chemical modifications and sequence engineering.

KEYWORDS:

• Immunotherapy
• cancer vaccines
• RNA
• vaccines

Article highlights

• Most RNA-based vaccines in the clinic are messenger RNA (mRNA), and RNA replicons (saRNA) have recently been studied.

• Chemically modification and sequence engineering have been used to increase the translation efficiency and stability of RNA-based vaccines.

• The combined administration of adjuvants and antigen encoding mRNA could provoke balanced adaptive immunity and innate immunity.

• RNA nanovaccines can offer new delivery routes, e.g., the intravenous route, and enable the modification of biological distribution, cellular targeting and cellular uptake mechanisms.

• TAAs and TSAs are used in RNA-based vaccines, and recent studies have shown the potential benefit of the neoantigen-based individualized cancer vaccines.

This box summarizes key points contained in the article.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Acknowledgments

The authors thank Prof. Mohammad Abdollahi for his invaluable assistance. All authors have read and approved the final manuscript.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.