Clinical Study of Oncolytic Vaccinia VIrus Delivering Targeted CD19 in Vivo CAR-T/M Therapy for Refractory/Relapsed B-cell Lymphoma

Inclusion Criteria:

1. Age≥ 18 years old, up to 75 years old, male or female;
2. ECOG score 0-2;
3. Histologically confirmed non-Hodgkin B-cell lymphoma (NHL) \[diagnostic criteria are WHO2008\], including diffuse large B-cell lymphoma (DLBCL) non-specific, primary mediastinal large B-cell lymphoma (PMBCL), mantle cell lymphoma (MCL), transformed follicular cell lymphoma (TFL) and other indolent B-cell NHL transformed types;
4. CD19 positive (immunohistochemistry or flow cytometry);
5. DLBCL refractory or relapse is defined as: complete remission after 2 lines of therapy; Disease progression during any course of treatment, or disease stabilization time equal to and less than 6 months; or disease progression or recurrence within 12 months after autologous hematopoietic stem cell transplantation;
6. MCL: Complete remission after 2 lines of treatment (including BTK inhibitors); Disease progression during any course of treatment, or disease stabilization time equal to and less than 6 months; or disease progression or recurrence within 12 months after autologous hematopoietic stem cell transplantation;
7. At least one measurable superficial lesion, requiring any length diameter of lymph node lesion greater than 1.5cm or any length diameter of extranodal lesion greater than 1.0cm, and uptake of the lesion on PET-CT scan (SUV greater than hepatic blood pool);
8. Absolute peripheral blood neutrophil ≥ 1000/mm3, platelet ≥ 50,000/mm3;
9. Heart, liver and kidney function: creatinine \<1.5mg/dL; ALT (alanine aminotransferase)/AST (aspartate aminotransferase) less than 2.5 times the upper limit of normal; Total bilirubin \< 1.5 mg/dL; Cardiac ejection fraction (EF) ≥ 50%;
10. Have sufficient understanding ability and voluntarily sign the informed consent form;
11. Women of childbearing potential must have a negative serum pregnancy test and agree to practice effective birth control during the treatment phase and for 60 days after the last application of oncolytic virus;
12. Male patients must agree to practice effective birth control during the study and for 60 days after the last viral treatment.

Exclusion Criteria:

1. History of other tumors;
2. Vaccination with the smallpox vaccine within 3 months before or during the study treatment;
3. Receiving gene therapy or any type of oncolytic virus therapy within 3 months before the study treatment;
4. Other open wounds;
5. Active autoimmune diseases;
6. Uncontrolled active infections;
7. HIV infection, uncontrolled HBV, HCV, or syphilis infection;
8. Known central nervous system lymphoma;
9. Clinically significant heart disease;
10. Allergy to albumin or egg products;
11. History of organ transplantation or similar surgeries;
12. Need for systemic treatment for skin diseases;
13. History of severe systemic reactions or side effects after smallpox vaccination;
14. Known alcohol or viral dependence;
15. Pregnant or breastfeeding women.