Exploratory Study of a Novel Oncolytic Vaccinia Virus RGV004 in the Treatment of Refractory/Relapsed B-cell Lymphoma

1. Age ≥ 18 years old, the upper limit is 75 years old, there is no restriction on men and women;
2. ECOG score 0-1;
3. Histological diagnosis of non-Hodgkin B-cell lymphoma (NHL) [diagnostic criteria according to WHO2008], including diffuse large B-cell lymphoma (DLBCL) non-specific, primary mediastinal large B-cell lymphoma (PMBCL) , Mantle cell lymphoma (MCL), transformed follicles Cell lymphoma (TFL) and other indolent B-cell NHL transformants;
4. CD19 positive (immunohistochemistry or flow cytometry);
5. DLBCL refractory (refractory) or relapse is defined as: complete remission is not achieved after 2-line treatment; disease appears during any treatment Disease progression, or disease stable time equal to or less than 6 months; or disease progression or recurrence within 12 months after autologous hematopoietic stem cell transplantation;
6. MCL: Complete remission has not been achieved after 2-line treatment (including BTK inhibitors); disease progression during any treatment, or disease stable time equal to or less than 6 months; or within 12 months after autologous hematopoietic stem cell transplantation Disease progression or recurrence;
7. There is at least one measurable superficial lesion, and any long diameter of the lymph node lesion is greater than 1.5 cm or any long diameter of the extranodal lesion is greater than 1.0 cm, and the PET-CT scan lesion is ingested (SUV is greater than the liver blood pool);
8. Peripheral blood neutrophil absolute value ≥ 2000/mm3, platelet ≥ 50,000/mm3;
9. Heart, liver and kidney functions: creatinine \<1.5mg/dL; ALT (alanine aminotransferase) / AST (aspartate aminotransferase) below 2.5 times the upper limit of normal; total bilirubin \<1.5mg/dL; cardiac ejection fraction ( EF) ≥50%;
10. Have sufficient understanding and voluntarily sign the informed consent form;
11. Women with fertility must undergo a negative serum pregnancy test and agree to implement effective birth control measures during the treatment phase and within 60 days after the last application of the oncolytic virus;
12. Male patients must agree to implement effective birth control measures during the study period and within 60 days after the last viral treatment.

Exclusion Criteria:

1. There is a history of other tumors;
2. Inoculate vaccinia vaccine 3 months before the study treatment and during the study treatment period;
3. Have received 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. Active infection that cannot be controlled;
7. HIV infection, uncontrolled HBV, HCV, and syphilis infection;
8. Known lymphoma of the central nervous system;
9. Clinically important heart disease;
10. Allergic to albumin or egg products;
11. Have undergone similar operations such as organ transplantation;
12. Systemic treatment of skin diseases is required;
13. A history of severe systemic reactions or side effects after vaccinia vaccine injection;
14. Known dependence on alcohol or viruses;
15. Pregnant or lactating female patients