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.

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.

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.

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.