[Edaily NA EUN-KYUNG Reporter] Immune cells that have memorized the “face” of cancer cells circulate throughout the body to track down any remaining cancer cells after surgery. The “cancer vaccine” whose potential was demonstrated by Moderna in Phase 3 clinical trials is not a vaccine that prevents cancer with a single injection, but rather an anticancer drug that teaches immune cells how to fight cancer to prevent recurrence. With a personalized messenger RNA (mRNA) cancer vaccine crossing the threshold into late-stage clinical trials for the first time, observers say the therapeutic cancer vaccine market—which has undergone decades of trial and error—has reached a turning point.

Moderna (ticker: MRNA) and Merck (MSD) announced on the 19th (local time) that the Phase 3 clinical trial “INTerpath-001” for melanoma—which combined the personalized mRNA therapy “Intismeran Autogen” in combination with the immunotherapy Keytruda met the primary endpoint of recurrence-free survival and the key secondary endpoint of distant metastasis-free survival. This marks the first instance of a personalized neoantigen therapy and an mRNA cancer therapy both succeeding in a Phase 3 clinical trial. Moderna’s stock price surged 177% on the day of the announcement not only because of the success of a single melanoma treatment but also because it confirmed the potential to expand mRNA technology to cancers such as lung, bladder, and kidney cancer.

In the official investor content “IR Insights,” released immediately after the announcement of the Phase 3 clinical trial results on the 19th (local time), Moderna CEO Stéphane Bancel stated, “The idea of creating mRNA therapies tailored to individual patients’ cancers has long been little more than a dream, but we have now begun to turn that dream into reality,” and “This achievement goes beyond a single pipeline and demonstrates the potential for an entirely new class of drugs,” he said, expressing his deep emotion at seeing years of research bear fruit.

An Anticancer Drug Named After a Vaccine… Imprinting Targets on Immune Cells

Intismeran differs from conventional drugs, which administer the same product to all patients. After analyzing a patient’s surgically removed tumor to identify mutations unique to cancer cells, an mRNA therapy containing up to 34 neoantigens is custom-made for each patient. When administered, immune cells learn to recognize these neoantigens as markers of cancer cells and seek out and attack cancer cells with the same characteristics.

In the pharmaceutical and biotech industries, the term “cancer vaccine” generally refers to this type of therapeutic cancer vaccine without further clarification. It falls into a different category from vaccines like “Gardasil” or “Cervarix,” which reduce the risk of developing cervical cancer. Cervical cancer prevention vaccines preemptively block infection with the human papillomavirus (HPV), which causes cancer.

In contrast, therapeutic cancer vaccines are anticancer drugs that introduce the immune system to antigens from cancer cells that have already developed. While cervical cancer vaccines use antigens from the virus that causes cancer, therapeutic cancer vaccines utilize antigens expressed by cancer cells. Although they share the term “vaccine,” they are fundamentally different types of medications.

Therapeutic cancer vaccines are, in a broad sense, classified as immunotherapy drugs. However, their role differs from that of immune checkpoint inhibitors—such as “Keytruda” and “Opdivo”—which are commonly referred to as immunotherapy drugs.

Immune checkpoint inhibitors block the “stop attack” signals that cancer cells send to T cells—a type of immune cell—allowing T cells to continue attacking the cancer cells. In contrast, cancer vaccines present the “wanted posters” of cancer cells to the immune system, thereby activating and proliferating T cells that identify and attack those specific cancer cells. No matter how much the brakes that block attacks are released, treatment efficacy may be limited if there are not enough T cells capable of recognizing cancer cells. This is why a combination strategy—using cancer vaccines to increase the number of T cells targeting cancer cells and using immune checkpoint inhibitors to remove the signals that block their attacks—is gaining attention.

Jeong Heon, CEO of Aston Science, a leading domestic cancer vaccine developer, explained in a phone interview with Edaily, “Immune checkpoint inhibitors block inhibitory signals so that T cells can kill cancer cells more effectively, while cancer vaccines ‘train’ T cells to recognize cancer cells.” He added, “Although their starting points are different, they ultimately share the common goal of using T cells to kill cancer cells.”

Combination of Cancer Vaccine and Keytruda… Rapid Attack and Long-Term Defense Simultaneously

Moderna also did not administer Intismeran as a monotherapy but combined it with Keytruda. The study compared an Intismeran-Keytruda combination group with a Keytruda monotherapy group in 1,137 patients with Stage 2B–4 melanoma who had undergone surgery. The combination group significantly prolonged the time to cancer recurrence or distant metastasis in all cases. No new safety concerns were identified.

Specific risk reduction rates from the Phase 3 clinical trial have not yet been disclosed. However, in the 5-year follow-up results from the preceding Phase 2b trial, the combination group showed a 49% lower risk of recurrence or death and a 59% lower risk of distant metastasis or death compared to the Keytruda monotherapy group. The two companies plan to continue monitoring overall survival while presenting detailed results at international conferences and discussing marketing authorization applications with regulatory agencies in various countries.

Immune checkpoint inhibitors help attack cancer cells relatively quickly, while cancer vaccines can maintain immunogenicity over the long term to ensure sustained efficacy. Because they play such different roles, a synergistic effect can be expected when used in combination.

Although estimates vary among market research firms due to differences in the scope of inclusion for HPV preventive vaccines and already commercially available immunotherapies, Future Market Insights projects that the global cancer vaccine market will grow from $12.6 billion (approximately 17.6 trillion won) in 2026 to $39.3 billion (approximately 58.8 trillion won) in 2036. Of this, therapeutic cancer vaccines are expected to account for 62.4% of the total market this year. In simple terms, this amounts to approximately $7.9 billion (about 11 trillion won).

From Antigen Identification to Clinical Trial Design… High Barriers to Entry

Cancer vaccine development is also underway in South Korea. Aston Science is developing AST-301, a plasmid DNA-based universal cancer vaccine that targets the HER2 antigen. Unlike Moderna’s personalized approach, which involves manufacturing a separate product for each patient, this method involves administering the same vaccine to multiple patients who express HER2.

AST-301 has completed patient dosing for a Phase 2 clinical trial aimed at obtaining approval for gastric cancer and is set to announce top-line results in the second half of this year. Aston Science has also confirmed the potential for combining AST-301 with Keytruda in preclinical studies and has adopted a clinical strategy for breast cancer that involves administering the vaccine alongside standard adjuvant therapies, such as Keytruda.

HLB INC.(028300)Immunomic Therapeutics, Aston Science’s U.S. subsidiary, is also developing cancer vaccines. Immunomic is developing ITI-5000, a self-amplifying RNA cancer vaccine based on its proprietary UNITE platform, as a treatment for triple-negative breast cancer. The company began dosing the first patient in a U.S. Phase 1 clinical trial last July and will sequentially evaluate both monotherapy and combination therapy with Keytruda.

In the past, companies such as Genexine, Inc.(095700)and the Cha Vaccine Research Institute (now ARIBIOLAB) also attempted to develop cancer vaccines. Genexine, Inc. completed a Phase 2 clinical trial for GX-188E, a DNA vaccine for HPV treatment, but decided to postpone pursuing conditional approval and a Phase 3 trial after considering market potential and the costs of late-stage clinical trials. The Cha Vaccine Research Institute also developed a cancer vaccine using the adjuvant “L-Pampo” up to the preclinical stage, but with management control recently transferring to AriBio, the focus of its R&D has shifted to the field of Alzheimer’s disease.

The primary reason cancer vaccine development is so challenging—to the extent that many pharmaceutical and biotech companies have attempted it only to put it on hold—is the need to identify antigens that can trigger a strong immune response while being distinguishable from normal cells. Even if a T-cell response to the antigen is confirmed, clinical trials must further demonstrate that it actually reduces tumor recurrence and mortality. Unlike conventional anticancer drugs, it takes time for the effects to manifest, making the clinical trial design—including defining the patient population and timing of administration—particularly complex.

CEO Jeong explained, “Personalized vaccines require the identification of neoantigens specific to each patient, while universal vaccines require the identification of antigens that are commonly expressed in the cancer cells of multiple patients and are easily recognized by T cells.” He added, “This is a field that requires not only the discovery of appropriate antigens but also clinical trial designs different from those of conventional anticancer drugs, necessitating the accumulation of expertise over a long period.”

Although domestic cancer vaccine development has struggled to gain momentum due to these high development hurdles, the market potential has been confirmed by Moderna’s successful Phase 3 trial, and the value of domestic developers currently conducting clinical trials is expected to be reevaluated.

Aston Science has also recently completed a Series D funding round worth 39.6 billion won and is preparing to make another attempt at going public. CEO Jeong said, “We plan to begin preparations for an initial public offering (IPO) in the second half of this year, timed to coincide with the announcement of the top-line results from the Phase 2 clinical trial of AST-301.”