mRNA therapeutics in cancer immunotherapy

Abstract

Synthetic mRNA provides a template for the synthesis of any given protein, protein fragment or peptide and lends itself to a broad range of pharmaceutical applications, including different modalities of cancer immunotherapy. With the ease of rapid, large scale Good Manufacturing Practice-grade mRNA production, mRNA is ideally poised not only for off-the shelf cancer vaccines but also for personalized neoantigen vaccination. The ability to stimulate pattern recognition receptors and thus an anti-viral type of innate immune response equips mRNA-based vaccines with inherent adjuvanticity. Nucleoside modification and elimination of double-stranded RNA can reduce the immunomodulatory activity of mRNA and increase and prolong protein production. In combination with nanoparticle-based formulations that increase transfection efficiency and facilitate lymphatic system targeting, nucleoside-modified mRNA enables efficient delivery of cytokines, costimulatory receptors, or therapeutic antibodies. Steady but transient production of the encoded bioactive molecule from the mRNA template can improve the pharmacokinetic, pharmacodynamic and safety properties as compared to the respective recombinant proteins. This may be harnessed for applications that benefit from a higher level of expression control, such as chimeric antigen receptor (CAR)-modified adoptive T-cell therapies. This review highlights the advancements in the field of mRNA-based cancer therapeutics, providing insights into key preclinical developments and the evolving clinical landscape.

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

“…Accelerated development, manufacture, clinical trials, and approvals of mRNA vaccines have been propelled in the past year by the COVID-19 pandemic [ 8 ]. An important outcome from the current interest in mRNA vaccines has highlighted their potential role in personalized medicine and therapeutics in oncology [ 13 ]. In the future, there will be increased collaboration between academic institutions, large pharmaceutical companies, and small biotech companies to develop and trial new mRNA vaccines.…”

“…In the future, there will be increased collaboration between academic institutions, large pharmaceutical companies, and small biotech companies to develop and trial new mRNA vaccines. Development of future tumor tissue-based laboratory diagnostics are likely to follow, with standardization, guidelines, and regulatory approval for the widespread use of these gene sequencing diagnostics in clinical laboratories as targeted mRNA vaccine therapy in oncology becomes increasingly available [ 13 ].…”

mRNA vaccines for infectious diseases: principles, delivery and clinical translation

“…Furthermore, these vaccines have elevated LNPs and RNA therapy from small-market products for niche diseases to a prophylactic treatment deployed successfully in large swathes of the population. The resultant abundance of positive safety and efficacy data, together with a proven path to regulatory approval, leave us optimistic that mRNA therapeutics will transform modern medicine’s approach to vaccination 1 , 5 , cancer immunotherapy 247 – 249 , protein replacement therapy 15 , 23 and beyond 250 .…”

Therapeutic cancer vaccines revamping: technology advancements and pitfalls

“…Importantly, gene-based vaccines have the potential to better target ITH compared to the other platforms by eliciting Ag-specific immune responses against different epitopes ( 58 ). This could be achieved by inserting sequences encoding for different NeoAg within each vaccination shot ( 59 ).…”

“…Novel delivery vehicles . Innovative compounds have been introduced in clinical trials, especially for RNA-based platforms, such as protamine combined, lipoplexes (LPX), or LNPs ( 58 ) ( 117 ). Among them, LNPs stand out as a major nanomedicine advancement, as witnessed by their implementation in the development of COVID-19 vaccines ( 65 ) ( 73 ).…”