Exploratory Study on the Treatment of EB Virus Positive HIV Associated Lymphoma With EBV mRNA Vaccine

Inclusion Criteria:

* 1\. Male or female patients aged ≥ 18 years during screening.
* 2\. Histological or cytological diagnosis of HIV associated lymphoma, including but not limited to diffuse large B-cell lymphoma (DLBCL), Burkitt lymphoma (BL), Hodgkin lymphoma (HL), etc.:

  1. Initial treatment population: patients who have not received systematic anti-tumor treatment;
  2. Relapse resistant population: patients who have received at least first-line treatment in the past and have experienced treatment failure or intolerance; Relapse is defined as the appearance of new lesions at the primary site or other locations after achieving complete remission (CR); Difficult to treat is defined as any of the following situations: (1) failure to achieve PR after ≥ 2 treatment cycles; (2) failure to achieve CR after ≥ 4 treatment cycles; (3) failure to achieve complete remission after autologous hematopoietic stem cell transplantation; (4) If the best therapeutic effect or end cause is PD, the number of cycles is not required (the same definition applies to relapsed/refractory lymphoma in the following text).
* 3\. Positive for EB virus infection (tissue EBER ISH/FISH testing).
* 4\. Complete at least 2 cycles of systemic chemotherapy without achieving CR (the initial treatment population must complete the entire chemotherapy course of the first-line treatment plan, unless intolerant).
* 5\. ECOG physical condition score: 0-2 points.
* 6\. Expected survival period ≥ 3 months.
* 7\. The main organ functions well, and the relevant examination indicators meet the following requirements:
* 8\. The subject has no pregnancy plan during the treatment period and agrees to voluntarily take effective contraceptive measures during the trial period and within 4 months of stopping treatment, and the pregnancy of women of childbearing age is negative.
* 9\. Able to understand and voluntarily sign a written informed consent form before the experiment.
* 10\. Able to communicate well with researchers and willing to follow the protocol to complete the experiment.

Exclusion Criteria:

* 1\. The patient has a history of other tumors, except for the cured skin basal cell carcinoma, skin squamous cell carcinoma, superficial bladder cancer, cervical carcinoma in situ, gastrointestinal intramucosal carcinoma and other malignant tumors that the researchers think can be included.
* 2\. Known to have aggressive NK cell leukemia or concomitant hemophagocytic syndrome.
* 3\. Known to have uncontrolled cardiac clinical symptoms or diseases, such as New York Heart Association (NYHA) grade II or above heart failure, unstable angina, myocardial infarction within 6 months, clinically significant and requiring treatment or intervention in patients with supraventricular or ventricular arrhythmias.
* 4\. Any active autoimmune disease or autoimmune disease history, including but not limited to immune related neurological disease, multiple sclerosis, autoimmune (demyelinating) neuropathy, Guillain Barre syndrome, myasthenia gravis, systemic lupus erythematosus (SLE), connective tissue disease, scleroderma, inflammatory bowel disease, including Crohn's disease and ulcerative colitis, autoimmune hepatitis, toxic epidermal necrolysis (TEN) or Stevens Johnson syndrome (except for type I diabetes mellitus using a stable dose of insulin).
* 5\. If there are any uncontrollable clinical diseases (such as respiratory, circulatory, digestive, nervous, hematological, urogenital, endocrine system diseases) or mental illnesses (such as depression, schizophrenia) or other major diseases that, according to the researcher's assessment, may hinder the provision of informed consent, interfere with the interpretation of the trial results, pose risks to the subjects participating in this trial, or otherwise affect the achievement of the trial objectives.
* 6\. Patients with a known history of interstitial pneumonia or highly suspected of having interstitial pneumonia; Patients with lung abnormalities that may interfere with the detection or management of suspected drug-related pulmonary toxicity during the trial period.
* 7\. Allergic to the experimental drug (including any excipients). Previous history of severe allergies to any medication, food, or vaccine, such as anaphylactic shock, allergic laryngeal edema, allergic dyspnea, allergic purpura, thrombocytopenic purpura, local allergic necrosis reaction (Arthus reaction), etc.
* 8\. Patients who have had less than 4 weeks or 5 half lives (whichever is shorter) since their last anti-tumor treatment, or whose anti-tumor treatment-related adverse reactions (excluding hair loss) have not recovered to NCI CTCAE ≤ 1 or baseline standards after previous anti-tumor treatments.
* 9\. Subjects who receive systemic therapy with corticosteroids (\>10 mg/day of prednisone or equivalent doses of other corticosteroids) or other immunosuppressive agents within 14 days or 5 half lives (whichever is shorter) prior to the first administration. In the absence of active autoimmune diseases, inhalation or topical use of steroids and adrenal hormone replacement with a dose ≤ 10 mg/day of prednisone therapeutic dose is allowed.
* 10\. Within 3 months prior to the first administration, have received mRNA vaccines or similar nanoparticles such as LNP for drug delivery.
* 11\. Previously received organ transplantation or allogeneic hematopoietic stem cell transplantation.
* 12\. Blood donation or significant blood loss (\>450 mL) within the first 3 months of screening.
* 13\. Those who have undergone major surgery within the 4 weeks prior to screening (excluding minor surgeries such as catheter placement or biopsy surgery as required by the protocol), or whose impact of surgery or trauma has been eliminated for less than 14 days prior to enrollment.
* 14\. Have a history of drug abuse or known medical, psychological, or social conditions, such as a history of alcohol or drug abuse.
* 15\. Known hepatitis B B virus, hepatitis C virus, and syphilis infection, or hepatitis B B surface antigen (HBsAg), hepatitis B core antibody (HBcAb), hepatitis C virus antibody (HCVAb), and treponema pallidum (TP) antibody were positive when screening: HBsAg (+) or HBcAb (+), and HBV DNA copy number ≥ 2000 IU/mL (or the lower limit of positive detection value in the research center); HCVAb positive and HCV RNA ≥ ULN of the research center.
* 16\. The patient has a history of active pulmonary tuberculosis (TB) or active TB; Or severe acute or chronic infections that require systemic treatment.
* 17\. Pregnant or lactating women.
* 18\. The researchers believe that there are any other factors that are not suitable for the subjects to enter this trial.