In recent years, RNA vaccines have attracted widespread attention for their potential in cancer treatment. With the successful rollout of COVID-19 vaccines, RNA technology has demonstrated its potential for rapid development and customization, bringing new hope to cancer treatment. The report “How personalized cancer vaccines could keep tumors from coming back” on June 11th in Nature discussed the application of RNA vaccines in personalized cancer treatment, especially their 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 enormous potential in cancer treatment. Through custom design, these RNA vaccines can train the immune system to target specific mutated proteins (neoantigens) in individual cancer patients, thereby effectively attacking the remaining tumor cells.
Cancer is one of the leading causes of death worldwide. Although traditional treatments such as surgery, radiotherapy, and chemotherapy have achieved certain results, they have severe side effects and high recurrence rates. In recent years, immunotherapy has become a new hope for cancer treatment by stimulating the patient’s own immune system to identify and destroy cancer cells. Among them, the successful application of mRNA vaccines in the development of COVID-19 vaccines has attracted widespread attention due to its rapid development and high degree of customization, and it has quickly turned to cancer treatment research.
Researchers developed a customized mRNA vaccine for melanoma patient Angela Evatt. The vaccine aims to train the patient’s immune system to recognize and attack remaining cancer cells by encoding specific mutant proteins (neoantigens).
Evatt’s treatment began with surgery to remove malignant melanoma from her back and lymph nodes in her left armpit. This operation is not only to remove cancerous tissue but, more importantly, to obtain tumor samples to create personalized vaccines. The researchers genetically sequenced the samples and identified specific mutant proteins. These mutated proteins are called neoantigens, which are present on the surface of cancer cells and can be recognized by the immune system.
The researchers then synthesized the mRNA encoding these neoantigens and prepared them into vaccines. The key to this process is ensuring that the mRNA can accurately enter the patient’s healthy cells and express the neoantigen within the cells, thereby triggering an immune response. To enhance the stability and effectiveness of the vaccine, the mRNA is encapsulated in lipid nanoparticles.
Evatt began receiving treatment with a personalized mRNA vaccine in March 2020. At the same time, she also received a combination treatment with an immune checkpoint inhibitor. Checkpoint inhibitors enhance the immune system’s attack power against cancer cells by blocking the immune system’s inhibitory signals. Every three weeks, Evatt travels from Maryland to Georgetown University’s Lombardi Comprehensive Cancer Center in Washington, D.C., to receive an injection in each arm.
Although Evatt experienced severe flu-like symptoms after each injection—fever, aches, and chills—her treatment results were remarkable. So far, she has been in remission for more than three years, an encouraging result for a melanoma patient.
In a clinical trial involving 157 participants, data showed that combining the vaccine with a checkpoint inhibitor reduced the risk of disease recurrence by nearly 50% compared with inhibitors alone. Additionally, vaccines have shown potential to extend patients’ lives. This research result was presented by Jeffrey Weber of New York University Langone Health at the world’s largest annual meeting of cancer biology and oncology experts held in Chicago on June 3, 2024. Professor Weber announced.
Although the preliminary results are encouraging, the researchers stress that further large-scale studies are still necessary. In order 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, another trial began for nearly 900 lung cancer patients. The purpose of these trials is to further verify the effectiveness of the vaccine and provide support for future marketing.
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. With post-surgery treatment, these vaccines are expected to train the immune system to recognize and destroy remaining 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 stage of cancer most amenable to vaccine treatment is a critical issue. Researchers are working to determine which cancer types and stages 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 the vaccine requires further study.
Second, improving methods for predicting the most potent neoantigens remains an important research direction. Currently, researchers are using artificial intelligence and machine learning technologies to extract information from a large amount of clinical and experimental data to optimize the design and production processes of vaccines. By continuing to improve these techniques, researchers hope to more accurately predict which neoantigens will be effective in stimulating immune responses.
In addition, although mRNA technology has made certain progress in current research, other vaccine technologies, such as DNA, peptides, and genetically engineered viruses, are also being continuously explored. Each technique has its own unique benefits and challenges, and researchers are looking for the best technique for different cancer types.
Overall, personalized mRNA vaccines open up a new path for cancer treatment. Although there are still many problems that need to be solved, its prospects are promising, and it may become an important part of cancer treatment in the future. Through continuous technological innovation and clinical research, personalized mRNA vaccines are expected to play an increasingly important role in cancer treatment and bring new hope to patients.
In the future, with the advancement of technology and in-depth research, personalized mRNA vaccines are expected to be applied to more cancer types and gradually promoted into clinical practice. Researchers will continue to work hard to optimize vaccine design and production processes to improve vaccine effectiveness and safety. At the same time, large-scale clinical trials are conducted to verify the long-term effects and potential risks of the vaccine and ensure its reliability and effectiveness in practical applications.
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