RNA in Cancer Immunotherapy: Unlocking the Potential of the Immune System

Abstract

Recent advances in the manufacturing, modification, purification and cellular delivery of ribonucleic acid (RNA) have enabled the development of RNA-based therapeutics for a broad array of applications. The approval of two SARS-CoV-2-targeting mRNA-based vaccines has highlighted the advances of this technology. Offering rapid and straightforward manufacturing, clinical safety and versatility, this paves the way for RNA therapeutics to expand into cancer immunotherapy. Together with ongoing trials on RNA cancer vaccination and cellular therapy, RNA therapeutics could be introduced into clinical practice, possibly stewarding future personalized approaches. In the present review, we discuss recent advances in RNA-based immuno-oncology together with an update on ongoing clinical applications and their current challenges.

Colorectal Cancer Immunotherapy: State of the Art and Future Directions

“…Since generating ex vivo DCs is time-consuming and expensive, various vaccine platforms have been studied in CRC to deliver tumor antigens to DCs in situ . These platforms mirror the strategies used for delivery of antigens and maturation stimuli to ex vivo DCs and include the use of autologous or allogeneic irradiated CRC cells, 106 peptides, 107 , 108 mRNA, 109 viral, 110 , 111 and bacterial 112 , 113 vectors often combined with adjuvants. 114 In general, these vaccines have been well-tolerated in clinical trials.…”

A Brief Overview of Cancer Vaccines

“…The global experience with RNA vaccines developed to limit SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection and COVID-19 (coronavirus disease 2019) has encouraged exploration and applications of the same technologies for cancer vaccines. An excellent comprehensive review of this area has recently appeared 24 . Novel chemistry used in SARS-CoV-2 RNA vaccines addresses many previous challenges that prevented preclinical study and clinical development, for example, stability, pharmacokinetics, immunogenicity, and more 25 .…”

“…An excellent comprehensive review of this area has recently appeared. 24 Novel chemistry used in SARS-CoV-2 RNA vaccines addresses many previous challenges that prevented preclinical study and clinical development, for example, stability, pharmacokinetics, immunogenicity, and more. 25 Although there remain pharmacological and toxicological concerns of interest, it is exciting to consider that vaccine approaches relying on the use of biologics and peptides might be converted to lower-cost, RNA-based approaches with their benefits in manufacturing, purification, storage, and delivery.…”

Involvement of lncRNAs in the tumor microenvironment: a new property of tumor immunity

“…Over the past decade, substantial efforts have been made towards the clinical application of RNA-based therapeutics. Approval of an mRNA-based vaccine against SARS-CoV-2 demonstrated the clinical feasibility, safety, and efficacy of such therapeutics 16 . These findings have paved the way for the application of RNA therapeutics in cancer immunotherapy.…”

“…Compared to conventional drug formats, RNA therapeutics has a regulatory role in cancer progression, mainly by controlling the levels of target protein expression. The most prevalent RNA therapeutics can be divided into two main groups: coding RNA in vitro transcribed-messenger RNA (iVT-mRNA); and self-amplifying RNA (SAM) and non-coding RNAs (ncRNAs), including lncRNA, circular RNA (circRNA), miRNA, small interfering RNA (siRNA), and antisense oligonucleotides (ASOs) 16 . Although these ncRNAs cannot be translated into proteins to perform oncogenic or suppressor functions as can coding RNAs, ncRNAs participate in cancer cell biology to varying degrees.…”