Moderna's 'Personalized Cancer Vaccine', Will it Open New Possibilities for Preventing Cancer Recurrence?

While most people think of vaccines as only for prevention, cancer vaccines focus on precisely training the immune system to treat cancer that has already occurred. A vaccine is a process of injecting antigen components to make the immune system remember a specific target, and then training it to immediately attack that target if it appears again. While the main purpose of vaccines against viruses or bacteria is to prevent infection, cancer vaccines target cancer cells already present in the body.

Cancer is a disease caused by gene mutations, and these mutations alter the protein structure of cancer cells. The immune system fundamentally recognizes and attacks foreign invaders or abnormal cells as 'foreign.' Proteins altered by cancer cell mutations can act as neoantigens that are recognized as 'foreign' by the immune system, becoming targets for an immune response.

Unlike vaccines for conditions like the common cold or coronavirus, which can be applied to all patients universally, cancer involves different gene mutations in each patient's cancer cells. Even lung cancer patients have unique mutation information in their respective cancer cells, making a uniform approach impossible. It's like being unable to draw a common sketch of a criminal. Therefore, a 'personalized' approach, which analyzes each patient's unique cancer mutation information to create a vaccine specifically tailored to them, is essential.

Personalized cancer vaccines are produced through three stages. First, cancer tissue must be obtained, either through surgery or biopsy. Second, DNA is extracted from the collected cancer tissue and the patient's normal tissue, and genes are analyzed using next-generation sequencing (NGS). What used to be a lengthy analysis process can now be done in a single day. Third, a personalized vaccine is manufactured based on the analyzed mutation information.

The process of analyzing individual cancer mutations involves comparing the gene sequences of a patient's normal cells and cancer cells. By using computers to analyze the differences between the two cell types, it is possible to quickly identify which gene mutations have occurred in the cancer cells. This process requires specialized data analysis techniques and is used to select neoantigens among the discovered mutations that can effectively induce an immune response.

In Moderna's clinical trials, the entire process from cancer tissue analysis to personalized vaccine production took a total of 6 weeks. For cancer patients, time for preventing recurrence after surgery is crucial, and waiting two years is practically impossible. The 6-week period presents a realistic timeline for administering the vaccine during the high-risk recurrence period after cancer surgery, thanks to advancements in mRNA technology.

mRNA technology is a core principle that dramatically speeds up vaccine development. Traditional methods required directly creating viral proteins through genetic engineering, which took at least two to three years. In contrast, mRNA delivers a 'blueprint' that instructs the body to create the desired protein, instead of creating the protein itself. When this blueprint is injected into the body, the body's cells directly produce cancer-specific proteins, allowing for much faster and easier production of personalized vaccines.

In this clinical trial, Moderna's cancer vaccine was used in combination with the immunotherapy drug Keytruda. This is because clinical trials need to compare the effectiveness of new treatments with current standard treatments to determine the degree of improvement. While the cancer vaccine teaches T-cells the characteristics of the cancer to attack, Keytruda acts to release the 'brakes' that cancer cells use to evade T-cell attacks. In essence, it's a strategy to maximize the synergy of the immune response by identifying the target for attack with the vaccine and removing the attack inhibitors with Keytruda.

Personalized cancer vaccines differ in nature from existing vaccines that aim to prevent viral infections. For example, cervical cancer vaccines aim to prevent cancer by blocking viral infection itself. However, Moderna's personalized cancer vaccine, currently under development, targets patients who already have cancer, focusing on training the immune system to recognize and attack specific mutations in cancer cells to treat the cancer. Therefore, it can be considered to fall within the realm of therapeutic agents.

The most realistic expected effect of personalized cancer vaccines is to prevent cancer recurrence after surgery. Cancer patients have a high risk of recurrence due to microscopic residual cancer even after surgery. If a vaccine is produced and administered within 6 weeks based on individual patient's cancer cell mutation information, it becomes a new therapeutic concept that can effectively prevent such recurrence. In other words, cancer vaccines have great potential as a prophylactic treatment after surgery.

The realization of personalized cancer vaccine technology is based on the development of three key technologies. First, Next-Generation Sequencing (NGS) technology has dramatically reduced the time for analyzing a patient's cancer cell genes. Second, mRNA technology has enabled fast and efficient production of customized vaccines. Third, the emergence of immunotherapy drugs (Keytruda) allows for maximizing vaccine effectiveness by blocking the 'brakes' that cancer cells use to evade immune responses. The synergy of these three technologies is a success factor in personalized cancer vaccine development.

Personalized cancer vaccines do not guarantee 100% effectiveness for all patients. Current clinical data show a limited percentage of complete treatment efficacy. This is because the technology for computer-based prediction of antigens that effectively stimulate an immune response is not yet perfect. For a vaccine to accurately stimulate T-cells to attack cancer cells, advancements in technology for precisely selecting which mutations will most strongly induce an immune response are needed. Improving prediction accuracy is one of the biggest challenges for this treatment method.

Unlike Moderna's method of finding all individual patient mutations to create custom vaccines, Professor Shin Eui-cheol of KAIST proposes a 'common mutation vaccine' with a lowered target. Analysis of colorectal cancer patient data revealed that 12 common mutations could cover over 40% of all colorectal cancer patients. If vaccines are pre-produced targeting such commonly found mutations, production costs and time could be significantly reduced compared to personalized vaccines.

Common mutation vaccines can be pre-produced as 'off-the-shelf' products rather than custom-made for each patient, significantly lowering production costs. According to Professor Shin Eui-cheol's calculations, this method can reduce the price to one-tenth that of personalized vaccines. Achieving price competitiveness can provide treatment opportunities to more patients, and immediate vaccine administration on the day of surgery can maximize effectiveness without missing the optimal treatment window.

The immune system operates with great precision, so if vaccine design is imprecise, it is difficult to elicit a proper immune response. Just as a perfectly tailored suit is comfortable, a vaccine must precisely match the patient's cancer cell antigens to be effective. If the antigens targeted by the vaccine do not precisely match the actual cancer cells, the immune system cannot effectively attack the cancer cells. This highlights the technical difficulty of the personalized vaccine approach and shows how important accurate antigen selection is.

Professor Shin Eui-cheol operates 'T-Cellogy,' a KAIST faculty startup, conducting research on common antigen vaccines. T-Cellogy is named after Professor Shin Eui-cheol's specialty, T-cell biology. The company has entered the final stage of review for support from the Korea Drug Development Fund and is pursuing the commercialization of common antigen vaccine technology that can complement Moderna's personalized model and benefit more patients.