mRNA Vaccines Could Transform Melanoma Treatment

In recent years, the potential of RNA vaccines in cancer treatment has attracted widespread attention. With the successful launch of the COVID-19 vaccine, RNA technology has demonstrated its potential for rapid development and customization, bringing new hope to cancer treatment. Recently, Nature's report "How personalized cancer vaccines could keep tumours from coming back" explored the application of RNA vaccines in personalized cancer treatment, especially its prospects in the treatment of melanoma.

In recent years, an exciting technological breakthrough has emerged in the field of cancer treatment - personalized RNA vaccines. The development of RNA vaccines not only provides an effective means for rapid response to the new coronavirus (COVID-19), but also demonstrates its great potential in cancer treatment. Through customized design, these RNA vaccines can train the immune system to target specific mutant proteins (neoantigens) of individual cancer patients, thereby effectively attacking residual tumor cells.

Researchers have developed a customized mRNA vaccine for melanoma patient Angela Evatt. This vaccine is designed to train the patient's immune system to recognize and attack residual cancer cells by encoding specific mutant proteins (neoantigens). During Evatt's treatment, she first underwent surgery to remove the malignant melanoma on her back and the lymph nodes in her left armpit. This operation was not only to remove cancerous tissue, but more importantly to obtain tumor samples to make personalized vaccines. Researchers sequenced the genes of these samples and identified specific mutant proteins. These mutant proteins are neoantigens, which exist on the surface of cancer cells and can be recognized by the immune system.

Subsequently, the researchers synthesized mRNA encoding these new antigens and prepared them into vaccines. The key to this process is to ensure that the mRNA can accurately enter the patient's healthy cells and express the new antigens in the cells, thereby triggering an immune response. In order to enhance the stability and effectiveness of the vaccine, the mRNA is encapsulated in lipid nanoparticles.

Evatt began treatment with a personalized mRNA vaccine in March 2020, and at the same time, she also received a combination treatment with an immune checkpoint inhibitor. Checkpoint inhibitors enhance the immune system's attack on cancer cells by blocking the immune system's inhibitory signals. So far, she has maintained remission for more than three years, which is an encouraging result for melanoma patients.

In a clinical trial involving 157 participants, data showed that the combination of vaccines and checkpoint inhibitors reduced the risk of disease recurrence by nearly 50% compared with inhibitors alone. In addition, the vaccine also showed the potential to prolong patient life. Although the preliminary results are encouraging, the researchers emphasized that further large-scale studies are still necessary. To verify these preliminary results, in July 2023, the research team launched a large-scale clinical trial involving more than 1,000 melanoma patients. A few months later, a trial of nearly 900 lung cancer patients began. The purpose of these trials is to further verify the effectiveness of the vaccine and provide support for future market promotion.

In addition to melanoma, researchers are also exploring the use of mRNA vaccines in other high-risk cancers such as colorectal cancer and pancreatic cancer. Through post-operative treatment, these vaccines are expected to train the immune system to recognize and eliminate residual cancer cells, thereby preventing the disease from returning.

Although personalized mRNA vaccines show great potential in cancer treatment, their success still faces many challenges. First, determining the cancer stage that is most suitable for vaccine treatment is a key issue. Researchers are working to determine which cancer types and stages can benefit most from this treatment. For some early-stage cancers, personalized mRNA vaccines can effectively prevent cancer recurrence, while for advanced cancers, the effectiveness of vaccines needs further study. Second, improving methods to predict the most effective new antigens remains an important research direction. Currently, researchers use artificial intelligence (AI) and machine learning (machine learning) technologies to extract information from a large amount of clinical and experimental data to optimize vaccine design and production processes. By continuously improving these technologies, researchers hope to be able to more accurately predict which new antigens can effectively stimulate immune responses.

In addition, although mRNA technology has made some progress in current research, other vaccine technologies such as DNA, peptides, and genetically engineered viruses are also being explored. Each technology has its own unique advantages and challenges, and researchers are looking for the best technology that is most suitable for different cancer types. Overall, personalized mRNA vaccines have opened up a whole new path for cancer treatment. Although there are still many problems to be solved, it has broad prospects and may become an important part of cancer treatment in the future.

Reference

Dolgin E. How personalized cancer vaccines could keep tumours from coming back. Nature, 2024, 630(8016): 290-292.