To evaluate the safety of therapeutic immunological agent against EBV-positive advanced malignancies, examining the incidence, type of occurrence, and severity of adverse events in relation to the agent tested, and initially exploring the effectiveness of the immunological agent.

EBV (Epstein-Barr virus) is the first tumor-associated virus to be discovered, closely related to a variety of malignant tumors, including nasopharyngeal carcinoma (NPC), a variety of lymphomas, such as Hodgkin lymphoma (HL), non-Hodgkin lymphoma (NHL), Burkitt's lymphoma (BL) and partial EBV positive stomach cancer (EBV-associated Gastric Carcinomas, EBVaGC). Treatment of the above EBV+ tumors, surgery, radiotherapy and chemotherapy are still the main methods, immunotherapy for some patients has shown good efficacy, prolonging the patient's overall survival rate (Overall Survival, OS) and progression-free survival rate (Progression-Free-Survival, PFS), but the overall clinical efficacy needs to be further improved, and new treatment methods are urgently needed.

After tumor cells are infected with EBV virus, they will express a variety of EBV virus antigens, which these proteins can promote the transformation and proliferation of human cells, inhibit cell apoptosis and participate in the occurrence and development of tumors, which also become candidate targets for research of immunotherapy because of the strong antigenicity of viral antigens.

Therapeutic immunological agent was prepared which are naturally loaded with EBV antigens and present them to activate T cells and dendritic cells(DC) in vitro and significantly inhibit tumor growth in vivo. The agent also showed good safety. According to these findings suggest the therapeutic immunological agent provides a new idea for immunotherapy of EBV-related tumors.

The findings suggest that a number of patients with malignant tumors who failed EBV+ multi-line therapy, including nasopharyngeal cancer, NK/T lymphoma, and gastric cancer needed to be treated with new immunotherapy method to achieve better outcomes.

Inclusion Criteria:

1. Male or female patients: ≥ 18 years old; ≤ 70 years old;

2. Patients with EBV-positive advanced malignant tumors after failure of second-line standard therapy (including PD-1 inhibitor therapy);

3. ECOG physical fitness score: 0~2 points;

4. Estimated survival ≥ 3 months;

5. The main organs have good function, that is, the relevant examination indicators within random 14 days meet the following requirements:

   1. Blood routine examination: hemoglobin ≥ 80 g/L (no blood transfusion within 14 days); Neutrophil count> 1.5×10^9/L; Platelet count≥ 80×10^9/L;
   2. Biochemical examination: total bilirubin ≤ 1.5× ULN (upper limit of normal); alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤ 2.5×ULN; If liver metastases are present, ALT or AST ≤ 5×ULN; Endogenous creatinine clearance ≥ 60 ml/min (Cockcroft-Gault formula);
   3. Cardiac Doppler ultrasound assessment: left ventricular ejection fraction (LVEF) ≥ 50%.

6. Sign the informed consent form;

7. Good compliance, family members agree to cooperate with survival follow-up.

Exclusion Criteria:

1. Participated in clinical trials of other drugs within 4 weeks;
2. The patient has a history of other tumors, unless it is cervical cancer in situ, treated cutaneous squamous cell carcinoma or bladder epithelial tumor or other malignant tumor that has received radical treatment (at least 5 years before enrollment)
3. Patients with uncontrolled cardiac clinical symptoms or diseases, such asheart failure above NYHA grade 2, unstable angina, myocardial infarction within 1 year, and clinically significant supraventricular or ventricular arrhythmias requiring treatment or intervention.
4. For female subjects: pregnant or lactating women.
5. The patient has active tuberculosis, bacterial or fungal infection; There is HIV infection with active HBV infection, HCV infection.
6. Those who have a history of psychotropic drug abuse and have mental disorders who cannot be remitted;
7. The subject has any active autoimmune disease or has a history of autoimmune disease (such as, but not limited to uveitis, enteritis, pituitary inflammation, nephritis, hyperthyroidism, hypothyroidism, Participants with vitiligo or who had complete remission of asthma in childhood and did not require any intervention in adulthood could be included; Participants in asthma requiring medical intervention with bronchodilators were not included).
8. According to the judgment of the investigator, there are concomitant diseases that seriously endanger the safety of patients or affect the completion of the patient's research.