[Edaily Reporter KIM JI-WAN ] A tumor disappeared after just a single dose. This is the result of preclinical research on KLS-3021, which KOLON LIFE SCIENCE Inc.(102940)presented last April at the American Association for Cancer Research (AACR 2026) conference. The study found that in some animals, tumors shrank to the point where they were no longer visible to the naked eye, and in models using human-derived cancer cells, all subjects survived until the end of the experiment.

The secret to its incredible “penetration” power lies in its fundamentally different structure

. A KOLON LIFE SCIENCE Inc. official stated, “The key to this study is that it simultaneously targeted the physical barriers and immunosuppressive environment established by the cancer, rather than the tumor itself,” adding, “KLS-3021 is designed not only to eliminate tumor cells but also to transform the environment surrounding the tumor into one that is favorable for anticancer activity.”

A oncolytic virus is a therapeutic agent that enters cancer cells, replicates inside them, and then destroys the cancer cells. The problem lies in its penetration ability. No matter how potent the therapeutic gene it carries, its effectiveness will inevitably be limited if it cannot spread throughout the entire tumor. In fact, many oncolytic virus candidates have been blocked by the barrier of diffusion within solid tumors.

KOLON LIFE SCIENCE Inc. found the solution in the therapeutic agent’s framework. Just as a car has an engine and a body, oncolytic viruses also have a virus that serves as their basic framework. In the pharmaceutical and biotech industries, this is referred to as a “backbone” virus.

KLS-3021 uses a vaccinia virus from the IHD-W lineage as its backbone instead of a standard vaccinia virus. This virus is known for its ability to travel farther and more extensively within tumors.

A KOLON LIFE SCIENCE Inc. official explained, “The IHD-W strain is characterized by its high viral spread capability,” adding, “The fact that it is designed to allow the therapeutic gene to function throughout the entire tumor is a key competitive advantage of KLS-3021.”

Actual tissue analysis also showed that the virus had spread beyond the tumor’s periphery and deep into its interior. However, the research team did not stop there.

This was because they determined that even if the virus entered the tumor, immune cells would still have difficulty accessing it as long as the “walls” built up by the cancer remained intact.

Breaking Down the Cancer’s Walls, Awakening the Immune System, and Stripping Away the Cancer’s Shield

The true distinguishing feature of KLS-3021 lies in the sequence in which it attacks the tumor. Most anticancer drugs target the cancer cells themselves. In contrast, KLS-3021 first breaks down the cancer’s defensive barrier.

Solid tumors create a structure called the extracellular matrix (ECM) to protect themselves. Simply put, it’s a concrete wall surrounding the cancer cells. This barrier prevents immune cells and anticancer drugs from entering the tumor.

PH-20, incorporated into KLS-3021, breaks down hyaluronic acid, the key component of this barrier. In actual studies, hyaluronic acid levels decreased significantly after administration of KLS-3021. Conversely, the virus spread deeper into the tumor. There was a marked increase in evidence of immune cells entering the tumor.

A KOLON LIFE SCIENCE Inc. official analyzed, “It is possible that PH-20 weakened the tumor barrier, thereby enhancing viral spread and improving immune cell access.”

Once the path was cleared, the next phase began. The IL-12 loaded onto KLS-3021 activated the immune cells. Subsequently, sPD1-Fc blocked the signals that cancer cells use to deceive immune cells. In effect, this broke down the cancer’s walls, deployed the immune forces, and stripped away the cancer’s shield.

A KOLON LIFE SCIENCE Inc. official emphasized the significance of the discovery, stating, “Since solid tumors involve both physical barriers and an immunosuppressive environment, relying on a single mechanism has its limitations,” and added, “KLS-3021 integrates the functions of barrier removal, immune activation, and immune evasion blockade into a single platform.”

Penetrating Deep into the Core of the Tumor

The most striking finding in this study was the movement of immune cells. An immune response was also observed in the group treated with existing anti-PD-1 immunotherapy. However, that response stopped at the tumor’s periphery. Anti-PD-1 is an immunotherapy mechanism that restores the function of immune cells suppressed by cancer cells; representative treatments include Keytruda (pembrolizumab) and Opdivo (nivolumab).

The research team observed granzyme B, a marker of immune cell attack. This is a key cytotoxic protein used by T cells and NK cells when attacking cancer cells. In the anti-PD-1 group, granzyme B signaling was limited to the periphery of the tumor. In contrast, in the KLS-3021 group, it extended strongly into the center of the tumor. This indicates that immune cells penetrated deep into the heart of the tumor.

KOLON LIFE SCIENCE Inc. official commented, “These results suggest that activated immune cells effectively infiltrated the interior of the tumor and carried out their attack functions.”

In fact, the number of immune cells attacking the cancer increased, while the number of immune cells protecting the cancer decreased. Signaling molecules that attract immune cells to the tumor and signals that activate the immune response also increased together. The research team interpreted these changes as ultimately transforming the tumor microenvironment itself into a state favorable for anticancer activity.

Tumor Disappearance with a Single Dose

This technological distinction ultimately translated into efficacy. In a head and neck squamous cell carcinoma model, KLS-3021 demonstrated a clear dose-dependent anticancer effect across the entire dose range, from low to high doses. Notably, the group receiving the highest dose showed results that were virtually equivalent to complete remission.

A KOLON LIFE SCIENCE Inc. official stated, “A visual evaluation of tongue tissue 24 days after administration revealed that no tumors were observed in 4 out of 6 animals,” adding, “Significant tumor reduction was also confirmed in the remaining animals.”

In the PD-L1-positive model, the drug demonstrated superior efficacy compared to anti-PD-1 immunotherapy. The research team concluded that even with high PD-L1 expression, the effectiveness of immunotherapy may be limited if immune cells cannot penetrate deep into the tumor. In contrast, they assessed that KLS-3021 likely overcame this limitation by simultaneously breaking down the tumor barrier and activating the immune system.

In a refractory model with low PD-L1 expression, the drug was compared to cisplatin, a representative chemotherapeutic agent. While cisplatin is a drug that inhibits cancer cell proliferation by damaging their DNA, concerns regarding its toxicity and resistance have been consistently raised. The results were even more dramatic. In the group receiving weekly cisplatin, the tumor-suppressing effect was limited.

However, KLS-3021 induced tumor regression with just a single dose. No significant weight loss was observed during the study period. This confirms both its potent anticancer effect and relatively good tolerability.

Even more remarkable results were obtained in a model using human-derived head and neck cancer cells. All nine animals survived until day 93, the end of the experiment, and imaging tests showed that tumor signals had disappeared.

A KOLON LIFE SCIENCE Inc. official stated, “Based on preclinical criteria, this represents complete remission (CR—a state where the tumor is no longer detectable on imaging),” adding, “Consistent efficacy was confirmed across three head and neck cancer models with distinct characteristics.”

The spokesperson emphasized, “This study does not simply mean that we succeeded in killing the tumor,” adding, “The results demonstrate the potential to break down the ‘fortress’ built by the cancer and allow immune cells to penetrate to the core of the tumor.”

The spokesperson added, “KLS-3021 is expected to set a new standard for oncolytic virus therapy.”