This study will test whether anti-EBV autologous TCR-T cell injection is safe and effective for patients with relapsed or refractory EBV-positive lymphoma who have HLA-A11:01. Researchers will look at safety, tolerability, and the maximum tolerated dose or recommended dose for future studies.
The study will also measure how the infused TCR-T cells expand and persist in the body, changes in EBV DNA levels and T-cell subgroups in the blood, and whether the treatment shows early signs of clinical benefit. Researchers will also explore whether the treatment causes an immune response against the infused cells.
Age 18-70 years, male or female.
HLA genotype at locus A is 11:01.
Histologically or cytologically confirmed EBV-positive lymphoma (tumor tissue must be EBER-positive as confirmed by in situ hybridization [ISH] or fluorescence in situ hybridization [FISH]), with peripheral blood EBV viral load >10³ copies/mL by quantitative real-time PCR.
Definition of relapse: appearance of new lesions at the primary site or other sites after achieving complete remission (CR).
Basal cell carcinoma of the skin;
Squamous cell carcinoma of the skin;
Superficial bladder cancer;
Carcinoma in situ of the cervix;
Single group
EBV TCR-T
DrugAfter signing the informed consent form and completing screening according to the inclusion/exclusion criteria, eligible subjects will be sequentially assigned to the following dose cohorts of TCR-T cells (single administration): 1×10⁶ TCR-T cells/kg, 2.5×10⁶ TCR-T cells/kg, 5×10⁶ TCR-T cells/kg, and 10×10⁶ TCR-T cells/kg. The first dose cohort (1×10⁶ TCR-T cells/kg) will use a rapid titration approach. If no significant safety issues occur within 28 days after infusion-defined as ≥Grade 3 non-hematologic toxicity, Grade 4 hematologic toxicity lasting more than 28 days (excluding disease- or chemotherapy-related causes), ≥Grade 2 neurotoxicity, or ≥Grade 3 cytokine release syndrome (CRS)-the next dose cohort will be initiated. If a dose-limiting toxicity (DLT) occurs, evaluation will be performed after 6 subjects have been treated. The subsequent three dose cohorts will follow a "3+3" dose-escalation design, with 3-6 subjects per cohort receiving a single infusion. For subjects in th
Dose-Limiting Toxicity (DLT)
To evaluate the incidence of dose-limiting toxicities (DLTs) of anti-EBV TCR-T cell injection in subjects with relapsed/refractory EBV-positive HLA-A11:01 lymphoma.
Maximum Tolerated Dose (MTD)
Determination of the maximum tolerated dose of anti-EBV TCR-T cell injection.
Recommended Phase 2 Dose (RP2D)
Determination of the recommended dose for the expansion study based on safety, tolerability, and MTD.
Expansion and persistence of EBV TCR-T cells
To evaluate the in vivo expansion and persistence of anti-EBV TCR-T cells after infusion
EBV DNA copies in peripheral blood
To evaluate the EBV DNA copy number in peripheral blood after infusion of anti-EBV TCR-T cells.
Changes in T-cell subsets in peripheral blood
To evaluate the changes in peripheral blood T-cell subsets after infusion of anti-EBV TCR-T cells.
Objective Response Rate (ORR)
Proportion of subjects achieving complete response (CR) or partial response (PR) following treatment with anti-EBV TCR-T cells.
Pharmacokinetic (PK) parameters
Maximum concentration (Cmax), time to maximum concentration (Tmax), and area under the curve (AUC0-28d) of anti-EBV TCR-T cells in peripheral blood.
Pharmacodynamic (PD) parameters
plasma cytokine levels at multiple time points after infusion.
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