PD-1 Knockout EBV-CTLs for Advanced Stage Epstein-Barr Virus (EBV) Associated Malignancies

A Phase I/II Trial of PD-1 Knockout EBV-CTLs for Advanced Stage EBV Associated Malignancies

This study will evaluate the safety of PD-1 knockout EBV-CTL cells in treating EBV (Epstein-Barr virus) positive advanced stage malignancies. Blood samples will also be collected for research purposes.

This is a study of CRISPR-Cas9 mediated PD-1 knockout-T cells from autologous origin. Patients are assigned to receive 4 circles of cell therapy. The safety and clinical response are evaluated. Biomarkers and immunological markers are also monitored.

Inclusion Criteria:

• Pathologically verified stage IV gastric carcinoma, nasopharyngeal carcinoma and lymphoma with measurable lesions (At least one measurable lesion or the immunotherapy)
• Pathologically verified as EBV positive malignancies
• Human leukocyte antigen (HLA) genotypes: HLA-A02, HLA-A24 or HLA-A11 genotypes
• Progressed after standard treatment or the patients refused to accept the standard treatment
• Performance score: 0-1
• Expected life span: >= 3 months
• Toxicities from prior treatment has resolved. Washout period is 1 months
• Major organs function normally
• Women at pregnant ages should be under contraception
• Willing and able to provide informed consent

Exclusion Criteria:

• Patients with possible drug allergy of immunotherapy
• Patients with active bacterial or fungal infections
• Coagulopathy, or ongoing thrombolytics and/or anticoagulation
• Blood-borne infectious disease, e.g. hepatitis B, hepatitis C and HIV
• History of coronary artery disease, asthma, or vascular disease or other disease inappropriate for treatment deemed by treating physician
• With other tumors except for in situ cervical cancer, treated squamous cell carcinoma and bladder cancer (Ta and TIS) or other malignancies that have been treated with radical therapy (at least for 5 years before the enrollment)
• With other immune diseases, or chronic use of immunosuppressants or steroids
• Pregnant and lactating women
• Compliance cannot be expected
• Other conditions requiring exclusion deemed by physician