From left: Professors Yang Yoo-soo and Kwon Dae-hyuk of Sungkyunkwan University, researcher Kim Ye-ri of the Korea Institute of Science and Technology, and researcher Park Won-beom of Sungkyunkwan University. Courtesy of Sungkyunkwan University.
A new type of messenger RNA (mRNA) cancer vaccine has been developed that blocks cancer cells from evading attacks by the human immune system. This achievement by a South Korean research team suggests the potential for mRNA vaccines, famously used during the COVID-19 pandemic, to be applied in cancer therapy.
Sungkyunkwan University announced on the 24th that a research team led by Professors Kwon Dae-hyuk and Yang Yoo-soo of the Department of Convergence Biosystems Engineering, in collaboration with the biotech company ‘MVRIX,’ has developed a dual-target mRNA cancer vaccine platform that simultaneously targets dendritic cells and cancer cells. The research findings were published in the international academic journal ‘ACS Nano’ on the 17th.
An mRNA cancer vaccine is a therapy that trains the body’s immune system to attack cancer by introducing mRNA containing information about cancer cells. Conventional vaccines delivered mRNA only to dendritic cells, which act as the command center for the immune response. This method relies on dendritic cells learning the cancer cell’s information and then issuing attack commands. However, if cancer cells engage in ‘antigen escape’—eliminating the target information recognized by the vaccine—the immune system can no longer identify the cancer cells, causing a sharp drop in therapeutic efficacy.
The research team focused on the ‘DEC-205’ protein, which is abundant on both dendritic cells and cancer cells, such as those in pancreatic and bladder cancer. DEC-205 is a protein found in large quantities on the surfaces of both cell types. The team designed the vaccine to use DEC-205 as a guide, allowing it to reach both types of cells simultaneously.
The mRNA that arrives at dendritic cells instructs the immune system to attack cancer cells, while the mRNA that reaches cancer cells forces them to produce the target protein themselves and display it on their surface. This means that even if a cancer cell hides its target, the vaccine forces it to be remade, fundamentally blocking the problem of antigen escape, a key weakness of previous vaccines.
The team equipped lipid nanoparticles (LNPs)—microscopic fat capsules that carry mRNA to cells—with an antibody that seeks out DEC-205. By leveraging the properties of cholesterol-transporting proteins in the blood, they enabled the antibody to self-assemble onto the capsule’s surface, allowing for production without complex chemical processing. The capsules delivered significantly more mRNA to tumor tissue than conventional methods.
Animal studies confirmed both the anti-cancer effects and recurrence prevention capabilities of the dual-target vaccine. When administered twice to animals with colorectal cancer, there was a significant increase in cancer-attacking T-cells, resulting in a powerful tumor-suppressing effect. In animals with breast cancer, survival time was also significantly extended, and no toxic side effects were observed.
Notably, when cancer cells were reintroduced after tumor removal, the cancer did not regrow in the vaccinated group. This indicates that ‘immune memory’ was established, where the immune system remembers the cancer cells and prevents recurrence.
Professor Yang Yoo-soo stated, “We have incorporated two strategies into a single platform: educating immune cells about the target while simultaneously forcing cancer cells not to hide it.” He added, “We plan to develop this into a next-generation immuno-oncology strategy tailored to the characteristics of individual patients.”
doi.org/10.1021/acsnano.5c20535
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