Editor's Note: Epstein-Barr virus (EBV) infection is widespread among adults, yet there is no standard treatment for EBV-positive hematologic malignancies, leading to poor patient outcomes. At the 29th Annual Meeting of the European Hematology Association (EHA), Professor Chunrui Li from Tongji Hospital of Huazhong University of Science and Technology presented the results of her team’s Phase I exploratory trial of the KSD-101 dendritic cell vaccine in treating EBV-related hematologic malignancies. This study brings new hope for treating these diseases. Oncology Frontier-Hematology Frontier interviewed Professor Li to delve into this innovative research and discuss the potential impact of KSD-101 on the future of hematologic malignancy treatment.Oncology Frontier-Hematology Frontier: At this EHA conference, you presented a study on the dendritic cell-based vaccine (KSD-101) for treating EBV-related hematologic malignancies. Could you briefly introduce KSD-101 and the motivation behind this research?
Professor Chunrui Li: EBV infection is prevalent worldwide, with over 95% of adults infected. However, there is a lack of awareness regarding EBV-related hematologic diseases, and no standard treatment is outlined in the NCCN and CSCO guidelines. Treatments for EBV-positive and EBV-negative patients are often similar, but EBV-positive patients have poorer prognoses, higher relapse rates, and increased mortality. Therefore, new treatments for EBV-positive hematologic malignancies are urgently needed.
KSD-101 is an autologous dendritic cell vaccine loaded with EBV-associated tumor antigens derived from human monocytes. Monocytes are induced into dendritic cells with cytokines, loaded with tumor antigens, and matured into dendritic cell vaccines. These vaccines, administered subcutaneously, activate EBV-specific cytotoxic T lymphocytes (CTLs) in the body to effectively recognize and kill tumor cells. This Phase I exploratory trial marks the first human study of KSD-101 for EBV-related hematologic malignancies. The primary goal is to evaluate the safety and preliminary efficacy of KSD-101 as a novel cellular drug and to establish the foundation for future research, such as determining the recommended dosing regimen for Phase II clinical trials.
Oncology Frontier-Hematology Frontier: What were the safety and efficacy outcomes of KSD-101 in this Phase I clinical study? How do you evaluate the potential impact of these initial results on subsequent research and clinical applications?
Professor Chunrui Li: The results presented at this EHA meeting reflect observations within 84 days post-vaccination. This Phase I trial included EBV-related hematologic malignancy patients who did not respond to conventional treatments or relapsed. Patients received subcutaneous KSD-101 monotherapy every two weeks for three to five injections without prior lymphodepletion or preventive medication. The study used a 3+3 dose-escalation design. As of October 30, 2023, nine patients had received at least three doses of KSD-101. Among the five evaluable patients (one was excluded due to early relapse, two were not yet evaluable, and one was excluded for other reasons), there were one case of angioimmunoblastic T-cell lymphoma (AITL), one case of chronic active EBV infection (CAEBV), two cases of NK/T-cell lymphoma, and one case of diffuse large B-cell lymphoma (DLBCL). Target cells of EBV infection included T cells, B cells, and NK cells.
- Efficacy: Among the five evaluable patients, both the objective response rate (ORR) and complete response rate (CRR) were 100%. Post-KSD-101 vaccination, significant changes in levels and proportions of various lymphocytes and immune cells in peripheral blood were observed, indicating a strong antitumor immune response: EBV-specific CTLs peaked significantly (baseline average 0.30% vs. treatment week 12 average 2.47%); immune cell peaks also increased, including B cells (average increase 27.51 times), NK cells (average increase 1.68 times), and CD8+ T cells (average increase 2.38 times), while regulatory T cells (Tregs) significantly decreased (average reduction 53.05%). These results suggest that KSD-101 vaccination induces significant changes in immune cell counts, enhancing antitumor immune responses consistent with clinical efficacy.
- Safety: In the dose-escalation phase, three patients received 5.0×10^6 cells per dose, and two received 7.5×10^6 cells per dose. Based on safety, preliminary efficacy, and feasibility assessments, the third dose group was canceled, and 5.0×10^6 cells per dose were used in the expansion phase. No dose-limiting toxicity (DLT) or maximum tolerated dose (MTD) was observed in any patient. The vaccine was well-tolerated, with KSD-101-related toxicities including fever (grade 1-2), injection site reactions (grade 1), lymphadenopathy (grade 1), and increased lymphocyte count (grade 1).
- Conclusion and Clinical Impact: To date, KSD-101 has demonstrated good safety and efficacy, effectively activating the immune system. The study indicates that KSD-101 is a promising cellular drug for treating EBV-related hematologic malignancies. Larger prospective studies and longer follow-up periods are needed.
These preliminary results have significant potential implications for future research and clinical applications. First, they provide a solid foundation for further research on KSD-101, especially in determining optimal dosages and treatment regimens. Second, these results enhance our confidence in DC vaccines for treating EBV-related hematologic malignancies, offering new directions for future treatment strategies.
Oncology Frontier-Hematology Frontier: What are your plans for future research on KSD-101? What changes do you anticipate this vaccine will bring to the treatment of EBV-related hematologic malignancies? Could it potentially be applied to other types of hematologic malignancies or other diseases?
Professor Chunrui Li: The safety and efficacy of KSD-101 have been preliminarily validated in clinical IIT research and will soon enter the registration clinical phase. Future clinical trials will expand the sample size and set reasonable endpoints and treatment regimens (including combination therapies) according to specific research goals, refining target populations (considering tumor types, severity, etc.) to fully evaluate KSD-101’s clinical value and support product registration and commercialization. If these positive results are confirmed in larger clinical trials, KSD-101 could transform the treatment of EBV-related lymphoproliferative diseases.
On March 30, 2024, KSD-101 received Investigational New Drug (IND) approval from the U.S. Food and Drug Administration (FDA), becoming China’s first original dendritic cell vaccine (DC vaccine) to receive FDA IND approval. Early exploratory clinical research on KSD-101 for treating EBV-related nasopharyngeal carcinoma is also actively underway in China. We look forward to expanding KSD-101’s applications to other potential indications, efficiently advancing its registration, and providing more treatment options for cancer patients, ultimately benefiting a wider patient population.
Expert Profile
Professor Chunrui Li
- Chief Physician, PhD Supervisor, Secretary of the Party Branch and Deputy Director of Medical Services, Department of Hematology, Tongji Hospital, Huazhong University of Science and Technology
- Specialization: Immunotherapy for malignant hematologic diseases
- Member of the 11th Committee of the Hematology Branch of the Chinese Medical Association, Plasma Cell Disease Group
- Chairman of the Hematology (Hubei) Expert and Committee of the Geriatrics Branch of the Chinese Society of Gerontology and Geriatrics
- Standing Member of the Geriatrics Branch of the Chinese Society of Gerontology and Geriatrics
- Youth Committee Member of the Oncology Branch of the Chinese Medical Association
- Member of the Myeloma and Plasma Cell Disease Group of the 5th Hematologic Oncology Committee of the Chinese Anti-Cancer Association
- Youth Committee Member of the CSCO Anti-Leukemia and Anti-Lymphoma Alliance
- Deputy Chairman of the Hematology Branch of the Hubei Medical Immunology Society
- Principal Investigator of four National Natural Science Foundation projects; published over 20 SCI papers, including those in Blood, as the first author or corresponding author
