The mRNA COVID-19 vaccine has allowed us to witness the effectiveness, safety, and tremendous potential of mRNA technology. Currently, research institutions worldwide are targeting cancer as the next goal for mRNA technology. mRNA cancer vaccines work by generating proteins (tumor antigens) that are specifically expressed in cancer cells, activating cellular immunity to attack these cells. However, distinguishing between cancer cells and normal cells is challenging, and cancer cells possess immune-suppressive properties, making the development of mRNA cancer vaccines more challenging than mRNA vaccines for infectious diseases.
Therefore, enhancing the potency of mRNA cancer vaccines is necessary, and using adjuvants to boost immune activation is an effective strategy. However, if the adjuvant is too strong, adverse reactions can occur, and if it’s too weak, sufficient activation might not be achieved. Previous mRNA vaccines had adjuvant effects, but lacked a practical approach to achieving controlled adjuvant activity.
Researchers at the Nanomedicine Innovation Center at the Kawasaki Institute of Industrial Promotion in Japan have published a research paper titled “Comb-structured mRNA vaccine tethered with short double-stranded RNA adjuvants maximizes cellular immunity for cancer treatment” in the proceedings of the National Academy of Sciences (PNAS).
In this study, a novel mRNA structure was developed, combining a single-stranded mRNA sequence encoding antigens with double-stranded RNA (dsRNA) to create a comb-like structure. The single-stranded mRNA is responsible for antigen production, while the dsRNA acts as an adjuvant, further activating immune cells. This approach demonstrated high anti-tumor efficacy in melanoma and lymphoma mouse models. The intensity of immune stimulation could be controlled by adjusting the amount of dsRNA, allowing for controlled adjuvant activity that enhances vaccine efficacy while ensuring safety.
Furthermore, this comb-like mRNA structure can also be loaded into various mRNA vaccine delivery systems to enhance their effectiveness. The research team loaded the comb-like mRNA into lipid nanoparticle (LNP) systems used for delivering mRNA COVID-19 vaccines, as well as into polymer-based nanomicelles developed by the team itself. Both approaches resulted in improved vaccine efficacy. This demonstrates that the comb-like mRNA can serve as a straightforward and practical mRNA technology platform to safely enhance the therapeutic effects of various formulated mRNA cancer vaccines by independently controlling their adjuvant functions.
The crucial adjuvant functionality for mRNA cancer vaccines has not been precisely controllable or seamlessly integrated into vaccine design so far. As a result, researchers have had to rely on trial and error, testing numerous candidate compounds in animal experiments, which has complicated the vaccine development process. This latest study, however, directly incorporates the necessary and rational adjuvant functionality into mRNA vaccines through mRNA engineering. With this approach, adjuvant functionality can be easily incorporated into various mRNA vaccine delivery systems, thereby enhancing the effectiveness of cancer vaccines.
In summary, the research team has developed a novel mRNA structure—the comb-like mRNA—and demonstrated its effectiveness in various mRNA vaccine delivery systems. This comb-like mRNA serves as a versatile system to augment the efficacy of any mRNA vaccine under development. As the world accelerates the development of mRNA cancer vaccines as the next generation of cancer immunotherapy, comb-like mRNA holds promise as a core foundational technology to enhance their effectiveness.