EBV-AST Cell Injection for EBV-Associated Lymphoproliferative Disorders

Exploratory Clinical Study of EBV-AST Cell Injection for the Treatment of EBV-Associated Lymphoproliferative Disorders

This is an investigator-initiated, open-label, single-arm, dose-escalation exploratory study to evaluate the safety, tolerability, and preliminary efficacy of EBV-AST cell injection in adults with EBV-associated lymphoproliferative disorders, including post-transplant lymphoproliferative disease (PTLD) and EBV-positive lymphomas. Participants will receive EBV-AST cell infusions intravenously every 2 weeks for up to 3 infusions at escalating dose levels. The primary objective is to assess safety and determine a potential optimal biologically active dose. Secondary objectives include preliminary tumor response and EBV-related virologic outcomes, as well as cellular PK/PD.

Study Overview

• Status: Recruiting
• Conditions: Epstein-Barr Virus-Associated Lymphoproliferative Disorders; EBV-Positive Lymphoma
• Intervention / Treatment: Biological: EBV-AST Cell Injection

Detailed Description

EBV-associated lymphoproliferative disorders (LPD), including PTLD and EBV-positive lymphomas, are clinically challenging and may occur in immunocompromised or heavily treated patients. EBV-AST is a cellular immunotherapy consisting of EBV antigen-specific cytotoxic T lymphocytes generated by ex vivo stimulation and expansion of T cells using antigen peptide-loaded dendritic cells. After infusion, EBV-AST cells are expected to recognize and eliminate EBV-infected or EBV-antigen-expressing target cells and provide EBV-specific immune reconstitution.

This investigator-initiated, open-label, single-arm exploratory study uses a dose-escalation design to evaluate EBV-AST cell injection in adults with EBV-associated LPD. Approximately 4-18 participants will be enrolled across three dose levels (3×10^5, 3×10^6, and 3×10^7 cells/kg per infusion). EBV-AST will be administered by intravenous infusion every 2 weeks for up to three infusions, following protocol-defined escalation rules and DLT assessment within 28 days after the first infusion. Participants will be monitored for adverse events and immune-related toxicities, and assessed for preliminary efficacy (tumor response and EBV-DNA/virologic outcomes) and cellular PK/PD.

• Study Type: Interventional
• Enrollment (Estimated): 18
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Liping Dou; Phone Number: +8613681207138; Email: lipingruirui@163.com
• Study Contact Backup: Name: Daihong Liu; Phone Number: +8613681171597; Email: daihongrm@163.com

Study Locations

• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100853
      • Recruiting
      • Chinese PLA General Hospital
      • Contact: Daihong Liu; Phone Number: +8618301339032; Email: daihongrm@163.com
      • Contact: Email: daihongrm@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Able to understand and voluntarily sign written informed consent.
2. Age 18 to 75 years, inclusive.
3. HLA genotype matches at least one of the following: HLA-A02:01, HLA-A11:01, or HLA-A*24:02.
4. Karnofsky Performance Status (KPS) ≥ 70.
5. Life expectancy ≥ 3 months.
6. Diagnosed with EBV-associated lymphoproliferative disorders, including:
7. EBV infection-associated post-transplant lymphoproliferative disorder (PTLD) that is relapsed/refractory after at least first-line standard therapy; or
8. EBV-associated lymphoma confirmed by histology and/or cytology with EBER positivity (ISH/FISH), with no standard treatment available or not suitable for standard therapy, including but not limited to: EBV-positive DLBCL, EBV-positive NK/T-cell lymphoma, EBV-positive Hodgkin lymphoma, EBV-positive Burkitt lymphoma, EBV-positive nodal TFH lymphoma (AITL type), and EBV-positive primary cutaneous T-cell lymphoma, meeting protocol-defined relapsed/refractory criteria.
9. Absolute lymphocyte count ≥ 0.8 × 10^9/L (except for PTLD participants).
10. Adequate organ and bone marrow function per protocol-defined criteria.
11. Participants of childbearing potential agree to use highly effective contraception throughout the study; women of childbearing potential must have a negative pregnancy test at screening.

Exclusion Criteria:

1. Known hypersensitivity to the investigational product or its components.
2. Uncontrolled active graft-versus-host disease (GVHD) in PTLD participants.
3. Known primary immunodeficiency disorders (e.g., X-linked agammaglobulinemia, Wiskott-Aldrich syndrome, chronic granulomatous disease, hyper-IgE syndrome).
4. Severe uncontrolled medical conditions that, in the investigator's judgment, make the participant unsuitable for enrollment.
5. Serious cardiac disease within 6 months prior to first infusion (e.g., myocardial infarction, severe/unstable angina, bypass surgery, NYHA class III-IV heart failure).
6. Chronic diseases requiring systemic immunosuppressants or systemic steroids (except local/inhaled steroids or physiologic replacement therapy).
7. History of other malignancy within the past 5 years, except carcinoma in situ (e.g., cervix, bladder, breast) or non-melanoma skin cancer.
8. Receipt of lymphocyte-based immunotherapy (e.g., CIK, DC, DC-CIK, LAK) within 3 months prior to consent.
9. Receipt of interferon or other targeted immunodeficiency drugs within 3 months prior to consent; prior high-dose IL-2 therapy.
10. Anti-cancer therapy within 14 days prior to consent (including chemotherapy or immunosuppressants/steroids); other cell therapy or live vaccines/attenuated vaccines or other investigational drugs within 28 days prior to consent; curative radiotherapy or major surgery within 4 weeks, or palliative local radiotherapy within 2 weeks prior to consent.
11. Prior immune therapy-associated ≥ Grade 3 immune-related adverse events (irAEs).
12. Unresolved toxicity from prior therapy > Grade 1 (except alopecia any grade; peripheral sensory neuropathy ≤ Grade 2).
13. Uncontrolled psychiatric or neurologic disorders; drug abuse or alcohol dependence.
14. Positive HIV antibody; positive Treponema pallidum antibody; active hepatitis B (HBsAg and/or HBeAg positive with HBV-DNA above ULN) or active hepatitis C (HCV-Ab positive and HCV-RNA positive).
15. Uncontrolled severe active infection or contagious disease (excluding EBV infection).
16. Pregnant or breastfeeding women.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: EBV-AST Cell Injection; Participants with EBV-associated lymphoproliferative disorders (including PTLD and EBV-positive lymphomas) will receive EBV-AST cell injection by intravenous infusion in a dose-escalation scheme. EBV-AST is administered every 2 weeks for up to 3 infusions (Day 0, Day 14, and Day 28). Three dose levels are planned: 3×10^5, 3×10^6, and 3×10^7 cells/kg per infusion, with dose-escalation decisions based on safety and protocol-defined criteria.

Biological: EBV-AST Cell Injection; EBV-AST is an Epstein-Barr virus (EBV) antigen-specific cytotoxic T-lymphocyte product generated by ex vivo stimulation and expansion of T cells using peptide-loaded dendritic cells. EBV-AST is administered by intravenous infusion every 2 weeks for up to 3 infusions at escalating dose levels (3×10^5, 3×10^6, or 3×10^7 cells/kg per infusion), according to the protocol-defined dose-escalation design.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose-Limiting Toxicities (DLTs)	Number of participants experiencing dose-limiting toxicities (DLTs) within 28 days after the first EBV-AST cell infusion, as defined by protocol-specific criteria and graded according to NCI CTCAE v5.0.	From first infusion (Day 0) through Day 28
Safety: Incidence of Adverse Events	Number of participants with treatment-emergent adverse events (AEs), immune-related adverse events (irAEs), and serious adverse events (SAEs), graded according to NCI CTCAE v5.0, including clinically significant laboratory abnormalities.	From first infusion (Day 0) through 12 months after first infusion
Recommended/Optimal Biologically Active Dose (OBD)	Recommended/optimal biologically active dose (OBD) of EBV-AST, determined based on the incidence of DLTs, overall safety profile, and tolerability across dose levels.	Up to 28 days after first infusion for DLT evaluation; overall dose decision through study completion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	Objective response rate (ORR), defined as the proportion of participants achieving complete response (CR) or partial response (PR) according to protocol-defined response criteria.	From first infusion (Day 0) through 12 months after first infusion
Disease Control Rate (DCR)	Disease control rate (DCR), defined as the proportion of participants achieving complete response (CR), partial response (PR), or stable disease (SD) according to protocol-defined criteria.	From first infusion (Day 0) through 12 months after first infusion
Progression-Free Survival (PFS)	Progression-free survival (PFS), defined as the time from first EBV-AST infusion to documented disease progression or death from any cause.	From first infusion (Day 0) through 12 months after first infusion
Overall Survival (OS)	Overall survival (OS), defined as the time from first EBV-AST infusion to death from any cause.	From first infusion (Day 0) through 12 months after first infusion
Duration of Response (DOR)	Duration of response (DOR), defined as the time from first documented complete or partial response to disease progression or death.	From first documented response through 12 months after first infusion
EBV-DNA Negativity Rate	Proportion of participants achieving EBV-DNA negativity in peripheral blood as measured by quantitative polymerase chain reaction (qPCR).	From first infusion (Day 0) through 12 months after first infusion
Time to EBV-DNA Negativity	Time from first EBV-AST infusion to first documented EBV-DNA negativity in peripheral blood.	From first infusion (Day 0) through 12 months after first infusion
Change in EBV-DNA Level	Change from baseline in EBV-DNA levels in peripheral blood over time, as measured by quantitative polymerase chain reaction (qPCR).	From baseline through 12 months after first infusion
Maximum Concentration (Cmax) of EBV-AST Cells in Peripheral Blood	The highest measured absolute concentration of viable EBV-AST cells in peripheral blood following infusion, quantified by flow cytometry.	From first infusion (Day 0) through Day 28
Concentration of EBV-AST Cells in Peripheral Blood (Cmax)	Maximum absolute concentration of viable EBV-AST cells in peripheral blood post-infusion, quantified by flow cytometry. Unit of Measure: viable EBV-AST cells per microliter (cells/μL).	From baseline through Day 28 after first infusion

Collaborators and Investigators

• Sponsor: Daihong Liu
• Investigators: Study Chair: Daihong Liu, Chinese PLA General Hospital

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2025
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): June 1, 2027

Study Registration Dates

• First Submitted: December 25, 2025
• First Submitted That Met QC Criteria: February 26, 2026
• First Posted (Actual): March 4, 2026

Study Record Updates

• Last Update Posted (Actual): March 4, 2026
• Last Update Submitted That Met QC Criteria: February 26, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Adoptive T-cell therapy; EBV-associated lymphoproliferative disorder; EBV-positive lymphoma; Antigen-specific T cells
• Other Study ID Numbers: S2025-726-02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Due to privacy concerns and the sensitive nature of the participant data, individual participant data (IPD) will not be shared. Access to data will be strictly controlled and provided only if required by regulatory authorities.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No