Background

Conventional cancer treatments have struggled to overcome the challenge of cancer recurrence, even after complete tumor resection through surgery, due to the proliferation of residual cancer cells. Analysis suggests that because each patient's cancer cells carry unique genetic mutation patterns, a one-size-fits-all approach to drug prescriptions is unlikely to yield high efficacy. Another obstacle has been the inability to apply targeted therapies to patients without specific mutations.

Efforts to develop personalized drugs based on tumor information have continued, but have not yet reached commercialization due to technical limitations and high manufacturing costs. At this juncture, vaccines based on messenger RNA (mRNA) technology have emerged as a promising alternative. This technology delivers blueprints to cells in the body to synthesize specific antigens, thereby triggering rapid and precise immune responses.

A key figure who accelerated the development of this technology is Dolly Parton, the country music legend, who recently passed away at the age of 80 after battling cancer. In March 2020, she donated $1 million to the Vanderbilt University Medical Center (VUMC). This donation proved to be a valuable resource in supporting Moderna's Phase 1 clinical trial of an mRNA vaccine during the early stages of the coronavirus disease 2019 (COVID-19) pandemic. The mRNA platform technology, which contributed to pandemic mitigation, is now bearing new fruit by advancing into cancer treatment development.

Key Findings

Moderna and Merck (Merck, MSD) have released results from a Phase 3 clinical trial of a personalized mRNA cancer vaccine for patients with advanced melanoma who had their tumors completely removed through surgery. Approximately 1,100 patients participated in this trial. The researchers divided the participants into two groups: one group received monotherapy with the immune checkpoint inhibitor pembrolizumab, while the other group received a combination therapy of pembrolizumab and the personalized mRNA vaccine intismeran, which was jointly developed.

The clinical results showed that the group receiving both the vaccine and the immunotherapy had a longer period of survival without recurrence compared to the group receiving immunotherapy alone. Intismeran is a highly personalized treatment designed based on the patient's tumor sample. First, the genetic mutations in the patient's cancer cells are analyzed to identify neoantigens—unique proteins that can be targeted by the immune system. Moderna employs artificial intelligence (AI) tools to select neoantigens that are most likely to elicit a strong immune response. Using this information, a personalized mRNA vaccine is manufactured for each patient.

Once administered, the vaccine instructs the body's cells to express the selected neoantigen. Immune cells then recognize this neoantigen and are trained to target and attack cancer cells that display the same antigen on their surface. Unlike traditional targeted therapies, which administer the same drug to all patients with specific genetic mutations, intismeran represents a paradigm shift by manufacturing a unique pharmaceutical product for each individual patient.

Significance and Outlook

The success of this Phase 3 clinical trial demonstrates the potential of mRNA technology to evolve from a vaccine platform for infectious disease prevention into a full-fledged personalized disease treatment platform. This achievement lays the groundwork for developing personalized cancer vaccines not only for melanoma but also for various solid tumors. The personalized medical approach is expected to have a positive impact on the development of treatments for rare and intractable diseases characterized by unique genetic mutations.

However, there are still practical barriers to overcome before commercialization. It typically takes several months to complete the process of collecting a patient's tumor tissue, performing genetic analysis, predicting neoantigens, and manufacturing a personalized vaccine. For patients with rapidly progressing late-stage cancer, the survival period may expire before the vaccine is ready. Additionally, the manufacturing process is complex and not amenable to mass production, raising concerns about the high initial treatment costs.

Long-term follow-up observations are also necessary to verify whether the vaccine significantly contributes to patient survival rates. While the clinical results demonstrated the vaccine's ability to delay cancer recurrence, further years of observation will be required to determine whether it extends overall survival. Nevertheless, the leap in mRNA vaccine development, initiated by Dolly Parton's donation, has set a clear milestone in humanity's journey toward conquering cancer.