Clinical Study of EBV-TCR-T Cells for EBV Infection After Allogenic HSCT

Multicenter, Open Label, Single-arm Exploratory Clinical Study of EBV-TCR-T Cells for EBV Infection After Allogenic HSCT

This is a multi-center, single arm, open-label, phase I study to determine the safety and effectiveness of EBV-TCR-T cell immunotherapy in treating EBV virus infection after allogenic HSCT.

EB virus (EBV) infection after allogeneic hematopoietic stem cell transplantation (HSCT) is common and can be lethal without prompt treatment. In this prospective study, HLA-A*02:01/11:01/24:02-restricted EBV-specific T cell receptor (TCR) will be introduced into the T cells of HSCT donors by ex vivo lentiviral transduction to generate EBV-TCR-T cells. An escalated dose ranging from 3×10^5/kg to 1×10^6/kg of EBV-TCR-T cells will be infused into patients with EBV infection. The safety, efficacy, pharmacokinetics and cytokine levels of allogenic EBV-TCR-T cell therapy will be evaluated.

Inclusion Criteria:

• Age 14-75 years, gender unlimited.
• Diagnosed with hematologic malignancies and have undergone allogeneic hematopoietic stem cell transplantation (allo-HSCT), with EBV infection after allo-HSCT.
• Karnofsky Score ≥ 70(age ≥16y) or Lansky Score ≥ 50(age<16y).
• TCR-T cell donor inclusion criteria: 1) Age 8-70 years; 2) Understand and voluntarily sign informed consent and are willing to comply with laboratory tests and other research procedures; 3) ≥ 3/6 HLA match with TCR-T cell recipients enrolled; 4) Lymphocyte count = (0.8~4) × 10^9/L; 5) Have sufficient venous circulation, without any symptoms that do not allow blood cell isolation.

Exclusion Criteria:

• Patients with uncontrolled active aGVHD one day before TCR-T cell infusion.
• Patients with severe kidney disease (Cr > 3×normal value), liver damage (TBIL >2.5×upper limit of normal value, ALT and AST > 3×upper limit of normal value) or heart failure (NYHA heart function grade IV) one week before TCR-T cell infusion.
• Anticipated to take immunosuppressive hormones on the day of TCR-T cell infusion.
• Have other malignancies.
• Have relapsed and uncontrolled hematologic malignancies.
• Serologically positive for HIV-Ab or TAP-ab.
• Pregnant or lactating women.
• Anticipated to have other cell therapies in 4 week post TCR-T cell infusion.
• Participated in any other clinical study of drugs and medical devices before 30 days of enrollment.