mRNA Vaccines will Soon Prevent Cancer

In the early 1990s, mRNA technology emerged as an alternative to traditional vaccine development, building on research conducted by Wolff et al. involving direct gene transfer into mouse muscle in vivo. Initially, mRNA technology came with drawbacks as it caused severe inflammation upon administration, degraded quickly in the body and was difficult to move across the membrane into the cell. However, breakthroughs using nanotechnology overcame some of these challenges; scientists encased the RNA and used synthetic RNA that the body’s immune system recognizes.

Other major technological innovation and research investment has improved the delivery, translation and stability, enabling mRNA to become a promising tool for vaccine development. These breakthroughs have allowed further research and development of mRNA vaccines, particularly against viruses such as HIV and influenza. In 2020, when the COVID-19 pandemic hit, several human clinical trials were underway to test mRNA vaccines against influenza and HIV. As a result of the pandemic, research efforts, funding and facilities prioritized the development of mRNA vaccines for COVID-19. Combined efforts of global research teams working on COVID-19 mRNA vaccinations accelerated the field of research, improving the knowledge, understanding and methods of mRNA vaccine technology. This allowed the progression of mRNA vaccines for other diseases, such as cancer, and clinical trials for mRNA cancer vaccinations are now underway. The MD Anderson Cancer Center (TX, USA) is conducting a clinical trial to test whether mRNA technology can be used to prevent the recurrence of colorectal cancer.

A B cell displays antibodies specific to antigens on a colorectal cancer cell and signals killer T cells to destroy it.

People with colorectal cancer often undergo surgery to remove the cancerous tumor; however, cancer cells remain in the body and shed DNA into the bloodstream, which is known as circulating tumor DNA (ctDNA) and can cause further complications and metastasis. Van Morris and Scott Kopetz are leading the Phase II trial (NCT04486378) for a personalized mRNA cancer vaccine. People who have stage II or III colorectal cancer are given a blood test after their surgery to check for ctDNA. The patient’s tumor tissue is genetically profiled to identify mutations that fuel cancer growth. The tumor mutations are then ranked from the most to the least common to create a personalized mRNA vaccine for the patient. “We’re hopeful that with the personalized vaccine, we’re priming the immune system to go after the residual tumor cells, clear them out and cure the patient,” explains Morris.