[Edaily Reporter KIM JI-WAN ] “The role of VT-EBV-N is to ensure that treated patients do not have to return to the hospital and to help them achieve a near-complete recovery.”

Jeon Young-woo, a professor in the Department of Hematology and Oncology at Yeouido St. Mary’s Hospital, The Catholic University of Korea, explained the clinical value of “VT-EBV-N,” a treatment for EBV-positive extranodal NK/T-cell lymphoma, in this way.

BigenCell’s VT-EBV-N, a treatment for patients with EBV-positive extranodal NK/T-cell lymphoma, was approved by the Ministry of Health and Welfare last April as the first advanced regenerative medicine treatment plan in Korea.

EBV-positive extranodal NK/T-cell lymphoma is a rare blood cancer with a high risk of recurrence even after achieving complete remission—a state where no cancer cells are detectable following anticancer treatment. If the disease recurs, treatment options are drastically reduced, and the prognosis for survival worsens significantly. VT-EBV-N is an autologous cell therapy designed to prevent relapse by eliminating microresidual disease that may remain in the body after a patient has achieved complete remission.

Last month, Professor Jeon presented the long-term follow-up results for VT-EBV-N during an oral session at the American Society of Clinical Oncology (ASCO) Annual Meeting 2026 held in Chicago, USA.

The clinical results showed that the 4-year disease-free survival rate in the treatment group was 95.0%, and the overall survival rate was 100%. In the control group, these rates were 56.3% and 83.8%, respectively. Notably, the disease-free survival rate in the treatment group remained at 95.0% at both the 2-year and 4-year marks.

On the 13th, E-Daily conducted an in-depth interview with Professor Jeon to hear about the remarkable results of VT-EBV-N. The following is a Q&A.

△Is EBV-positive extranodal NK/T-cell lymphoma a disease with a high risk of recurrence even after achieving complete remission?

-Yes. In this clinical trial, the 4-year disease-free survival rate in the control group was 56.3%. This means that a significant number of patients who had achieved complete remission relapsed or experienced disease progression within 4 years.

EBV-positive extranodal NK/T-cell lymphoma is characterized by a high recurrence rate even after remission, and once it recurs, the prognosis for survival becomes extremely poor. The recurrences and disease progression observed in the control group can be seen as a direct reflection of this disease’s common yet lethal characteristics. Currently, there is no established standard consolidation therapy available to prevent recurrence after complete remission.

△To what extent did the long-term outcomes differ between the VT-EBV-N treatment group and the control group?

- The 4-year disease-free survival (DFS) rate in the VT-EBV-N treatment group was 95.0%. Compared to the control group’s rate of 56.3%, this represents a difference of 38.7 percentage points. Overall survival (OS) was 100% in the treatment group and 83.8% in the control group. In the control group, there were six deaths over the 4-year period. Most of these were due to disease recurrence and progression.

P-values indicating statistical significance were also confirmed at 0.0210 for DFS and 0.0205 for OS. Although the number of patients was not large—21 in the treatment group and 25 in the control group—due to the nature of this rare disease, statistical significance was achieved because the difference in efficacy between the two groups was very substantial.

△In the treatment group, only 1 out of 21 patients experienced disease progression. What risk factors were present in this patient?

- This patient was not among those who received VT-EBV-N immediately after their initial treatment. They achieved their second complete remission (CR2) only after experiencing one relapse and undergoing salvage chemotherapy, at which point they were administered VT-EBV-N.

The patient was elderly, over 60 years old, and had stage 4 disease. The patient also had elevated levels of lactate dehydrogenase (LDH), an enzyme released into the bloodstream when cells are damaged or destroyed. (Although LDH is not a marker specific to cancer, it is used as a prognostic indicator in lymphoma patients, suggesting a high tumor burden or disease activity.)

In addition, the patient’s ECOG status—which indicates the ability to perform activities of daily living—was poor. The ECOG is a scale that assesses the extent to which a patient can independently perform daily activities such as walking, working, eating, and personal hygiene; generally, a higher score indicates poorer overall health and reduced functional capacity.

Although it is difficult to draw definitive conclusions due to the small number of patients, VT-EBV-N may be more effective when administered immediately upon achieving complete remission with the first course of chemotherapy rather than after recurrence. In other words, it may be more advantageous to eliminate any remaining micrometastatic cancer cells early on to prevent recurrence, rather than treating the cancer after it has reappeared.

△What does it mean that both the 2-year and 4-year disease-free survival rates remained at 95.0%?

- It means the drug’s efficacy was not limited to the short term but persisted over the long term. Generally, relapses of blood cancers tend to occur primarily within the first 1 to 3 years following treatment. The fact that the DFS in the treatment group remained steady at 95.0% from 2 to 4 years suggests that the treatment may have suppressed relapse itself, rather than merely delaying the timing of relapse.

In solid tumors and blood cancers, maintaining complete remission for five years or more is generally considered to indicate a high likelihood of a cure. Given that the current survival curve has remained stable through the four-year mark, it is highly likely that long-term follow-up beyond five years will also show a positive trend toward a cure.

△What is the mechanism by which the administered EBV-specific T cells suppress recurrence over the long term?

-It is difficult to conclude simply that the initially administered T cells remain in the body for several years and prevent recurrence on their own. VT-EBV-N is more akin to a therapy that helps the patient’s immune system learn how to recognize and attack the Epstein-Barr virus (EBV).

The administered EBV-specific T cells directly attack tumor cells while also eliciting a response from other immune cells. During this process, the activity of CD8-positive T cells (cytotoxic T cells) and natural killer (NK) cells is enhanced, and some of these cells remain as memory T cells. Memory T cells continuously monitor for the reappearance of EBV antigens.

In fact, while EBV DNA levels—the measure of EBV genetic material in the blood—temporarily increased in some patients after treatment, the levels subsequently decreased without cancer recurrence. This suggests that the patients’ immune systems may have developed the ability to suppress EBV on their own. It is believed that this immune memory also played a role in maintaining a 4-year disease-free survival rate of 95.0%.

△Unlike CAR-T therapy, why were there no notable cases of severe immunotoxicity?

- CAR-T therapy involves attaching artificial receptors that detect cancer cells to the patient’s T cells and then re-infusing them. These cells aggressively attack any remaining cancer cells in the body. Since the treatment is highly effective, it can also trigger a strong immune response.

A typical side effect is cytokine release syndrome (CRS). When immune cells are activated all at once, symptoms such as high fever, low blood pressure, and difficulty breathing may occur. Additionally, neurological toxicity accompanied by confusion or speech disorders may develop.

In contrast, VT-EBV-N uses autologous T cells derived from the patient’s own blood. These T cells are cultured to recognize and attack the LMP1 and LMP2a antigens present on cancer cells associated with the Epstein-Barr virus (EBV).

Simply put, rather than indiscriminately attacking all cancer cells, this approach selectively targets cells bearing EBV markers. This means there is a relatively lower risk of broadly attacking normal cells as well.

The timing of administration is also different. VT-EBV-N is administered during complete remission (CR), when the cancer is no longer detectable following anticancer treatment. The goal is to eliminate any microscopic cancer cells that may remain in the body and prevent recurrence. Since treatment is administered when the number of cancer cells is very low, the likelihood of an excessive immune response is also relatively low.

In fact, during this clinical trial, not a single case of treatment-related adverse events of Grade 3 or higher or serious drug-related adverse events occurred. No specific safety concerns were identified even in elderly patients. The ability to reduce the risk of recurrence while minimizing the burden of severe side effects is considered a clinical advantage of VT-EBV-N.

△How are the current dosage and treatment schedule structured? Would increasing the dosage lead to better efficacy?

- In the clinical trial, 40 million cells were administered once weekly for 4 weeks, followed by a 4-week rest period, and then another 4 weeks of once-weekly administration. This constitutes a total of 8 doses.

Theoretically, increasing the dose or frequency could potentially improve efficacy. However, even with the current dose and schedule, the results showed a 4-year disease-free survival rate of 95.0% and an overall survival rate of 100%, with no severe treatment-related adverse events. Considering both the cost of the drug and treatment efficacy, we believe the current administration regimen strikes an appropriate balance between efficacy and safety.

△What has been the reaction from international researchers following the presentations at ASCO and EHA?

-Many researchers were surprised by the fact that patients with rare diseases were recruited within a relatively reasonable timeframe, and that the hypothesis—that eliminating residual EBV would reduce residual tumor cells and recurrence—was validated in a real-world clinical setting.

While various cell therapies, including CAR-T, are being developed for B-cell lymphomas, T-cell lymphomas present a high degree of difficulty in cell therapy development, making successful cases extremely rare. Naturally, there were many questions regarding the mechanism of action and potential applications of VT-EBV-N.

Questions regarding practical application also followed, such as whether there were any safety concerns in elderly patients and whether autologous cell therapies could be stably produced and supplied if the treatment were expanded to the global market. I believe the high level of interest stemmed from the fact that this represents rare, successful cell therapy data in T-cell lymphoma.

△What are the plans for additional Phase 3 clinical trials and future patient treatment?

-Generally, conducting a Phase 3 trial requires more than 100 patients—at least twice the number in the current trial. However, since EBV-positive extranodal NK/T-cell lymphoma is an extremely rare disease, recruiting a large number of patients is not practically feasible.

Taking this into account, we established a control group and adopted a double-blind design when preparing for this Phase 2 trial. Unlike a typical single-arm Phase 2 trial, we designed it with a structure that is effectively close to a Phase 3 trial. At this time, we do not plan to conduct a separate Phase 3 trial.

Instead, by utilizing South Korea’s Advanced Regenerative Medicine Program, we have received approval for a treatment plan to administer VT-EBV-N to approximately 15 patients for therapeutic purposes. We expect to begin treating the first patients as soon as the detailed administrative procedures with the relevant government agencies are finalized.

△If you had to summarize the clinical significance of VT-EBV-N in a single sentence, what would it be?

-It may not be a spectacular treatment like CAR-T that dramatically saves patients on the brink of death. VT-EBV-N is a drug that quietly supports patients who have already been treated and achieved complete remission.

EBV-positive extranodal NK/T-cell lymphoma has a very poor prognosis upon relapse, yet there is no standard treatment to prevent relapse after remission. This study is significant in that it establishes the basis for a safe and effective treatment option that can maintain remission achieved through first-line therapy, prevent relapse, and dramatically improve survival rates.