The Safety and Efficacy of Anti-EBV Autologous TCR-T Cell Injection for Treating Relapsed/Refractory EBV-positive Lymphoma Patients With HLA-A11:01
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.
• Disease diagnosis and status:
∙ 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.
‣ Disease types include but are not limited to:
∙ NK/T-cell lymphoma (NK/TCL); Peripheral T-cell lymphoma (PTCL); Other types.
‣ Definition of relapse: appearance of new lesions at the primary site or other sites after achieving complete remission (CR).
‣ Definition of refractory disease (meeting any of the following):
• No partial remission (PR) after ≥4 cycles of standard therapy; No complete remission (CR) after ≥6 cycles of therapy; Failure to achieve CR after autologous hematopoietic stem cell transplantation; If best response is progressive disease (PD) or treatment is discontinued due to PD, no minimum cycle requirement applies.
• Prior treatment requirements:
• a) For relapsed/refractory PTCL or NK/TCL, patients must have received at least one prior line of systemic therapy. For relapsed/refractory NK/TCL, patients must have received an asparaginase-containing regimen (patients with stage I/II nasal NK/TCL according to the CA staging system must have also received radiotherapy).
• Measurable disease: At least one measurable lesion according to the 2014 Lymphoma Response Evaluation Criteria:
∙ Nodal lesions: longest diameter \>15 mm on contrast-enhanced CT, MRI, or PET-CT;
‣ Extranodal lesions: longest diameter \>10 mm.
• Adequate organ function, defined as:
∙ Hematologic: absolute neutrophil count ≥1×10⁹/L; hemoglobin ≥70 g/L; platelet count ≥50×10⁹/L;
‣ Hepatic: ALT and AST ≤3× upper limit of normal (ULN) (≤5× ULN if due to lymphoma liver involvement); total bilirubin ≤1.5× ULN;
‣ Renal: serum creatinine ≤1.5× ULN;
‣ Cardiac: left ventricular ejection fraction (LVEF) ≥50%;
‣ Coagulation: fibrinogen ≥1.0 g/L; activated partial thromboplastin time (APTT) ≤1.5× ULN; prothrombin time (PT) ≤1.5× ULN.
• Expected survival \>3 months.
• ECOG performance status \<3.
• Contraception requirements:
∙ No pregnancy planned during the treatment period;
‣ Women of childbearing potential must have a negative pregnancy test and agree to use effective contraception during the study and for 4 months after the end of treatment.
⁃ Willingness to participate in the study, ability to sign informed consent, comply with the study protocol, and availability of peripheral venous access for lymphocyte collection.