CELL INTELLIGENCE · 肿瘤细胞治疗研究

Inclusion Criteria:

* 1\. With the patient's consent and signed informed consent form, willing and able to comply with the planned visits, research treatments, laboratory tests, and other experimental procedures;
* 2\. CD19 and/or CD22-positive follicular lymphoma (FL) confirmed by histology according to the WHO classification:

  1. The patient's disease is still evaluated as partial response (PR) after induction treatment with standard first-line chemotherapy regimen, or
  2. The patient's disease reaches complete response (CR) after induction treatment with standard first-line chemotherapy regimen, but there are high-risk factors at the time of onset;
* 3\. The possible high-risk factors for the patient's onset of the disease are as follows: Presence of at least one of the following high-risk features at diagnosis:

  1. Follicular Lymphoma International Prognostic Index (FLIPI-1) score of 3-5 or FLIPI-2 score of 3-5;
  2. Presence of any lymph node or extranodal mass \>6 cm in diameter;
  3. Significant infiltration of CD68+ or CD163+ macrophages by immunohistochemistry;
  4. Gene sequencing revealing TP53 or NOTCH1 mutation;
  5. Presence of 1p36 deletion or 1q amplification;
  6. Next-generation sequencing (NGS)-defined high-risk mutation-based 7-gene Follicular Lymphoma International Prognostic Index (m7-FLIPI) subtype.
* 4\. Age range from 18 to 85 years old, male or female;
* 5\. Subjects with physical fitness status scores ranging from 0 to 2 in the Eastern Cooperative Oncology Group (ECOG) in the United States;
* 6\. Expected survival period from the date of signing the informed consent form is greater than 3 months;
* 7\. HGB ≥ 60g/L;
* 8\. The absolute value of neutrophils in peripheral blood is ≥ 1000/μl, and the platelet count is ≥ 45000/μl;
* 9\. Liver and kidney function, as well as heart and lung function, meet the following requirements:

  1. Total bilirubin (TBIL) ≤ 1.5 times the upper limits of normal (ULN), except for subjects with Gilbert's syndrome;
  2. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 times ULN;
  3. Serum Creatinine (Cr) ≤ 1.5 times ULN or Creatinine Clearance Rate (CCr) ≥ 60mL/min, estimated based on the Cockcroft Gault formula;
  4. The left ventricular ejection fraction (LVEF) of the heart is ≥ 50%. Echocardiography (ECHO) confirms no pericardial effusion and no clinically significant arrhythmia;
  5. Baseline transcutaneous oxygen saturation under indoor ventilation\>92%;
  6. No clinically significant pleural effusion;
* 10\. Participants with pregnancy plans must agree to take contraceptive measures for a continuous period of 6 months from before enrollment in the study until the end of the study; If the subject is pregnant or suspected of being pregnant, the researcher should be notified immediately.

Exclusion Criteria:

* 1\. Have received any form of chimeric antigen receptor cell therapy or other genetically modified T cell therapy;
* 2\. Has a history of severe immediate hypersensitivity reactions to aminoglycoside antibiotics and other essential medications;
* 3\. Known history of human immunodeficiency virus (HIV) infection or active hepatitis B virus (HBV) infection, or any uncontrolled active systemic infection requiring intravenous antibiotics (active HBV infection is defined as:

  1. HBV DNA quantification ≥ 2000 IU/ml;
  2. ALT ≥ 2 times the normal upper limit value;
  3. Exclude hepatitis caused by the disease itself, medication, or other reasons; All three conditions must be met simultaneously. If a patient is diagnosed with active HBV infection at the time of initial diagnosis and becomes non active HBV infection after anti HBV treatment, they can be included in this study under the premise of sufficient anti HBV treatment;
* 4\. Non hematological tumors (such as lymphoma) associated liver and kidney dysfunction: ALT\>3 times the upper limit of normal, AST\>3 times the upper limit of normal, TBIL\>2 times the upper limit of normal, serum creatinine clearance rate\<30 mL/min;
* 5\. History of myocardial infarction, cardiac angioplasty or coronary stent implantation, unstable angina, active arrhythmia, or other clinically significant cardiovascular diseases within the 12 months prior to enrollment;
* 6\. Other serious medical diseases may have an impact on this study (such as diabetes, gastric ulcer, other serious respiratory and circulatory diseases, severe autoimmune diseases or congenital immune defects, severe infection and inability to be effectively controlled), as well as other diseases with high risk of disease change;
* 7\. Has a history of severe immediate hypersensitivity reactions to any medication necessary for use in this study; History of severe allergy to biological products (including antibiotics);
* 8\. Female subjects who are currently pregnant or breastfeeding (with potential risks to the fetus or infant from pre-treatment chemotherapy regimens);
* 9\. The researchers determined that the subjects were unable to complete all the required visit surveys or diagnostic procedures (including medium - and long-term follow-up visits) as per the study protocol, had poor willingness to participate in the study, were unwilling to join and fully comply with the study arrangements, and had insufficient compliance with the study by the subjects and their families. The decision-making power belongs to the researcher;
* 10\. The subjects who have previously suffered from other malignant tumors cannot be included in this study unless they are disease-free and have not received any form of anti-tumor treatment for at least 3 years (except for skin tumors of non malignant melanoma and in situ cancers occurring in the cervix, bladder, breast, etc.);
* 11\. History of receiving live vaccines within 6 weeks prior to initiating the pre-treatment plan;
* 12\. Those who have undergone large-scale surgical treatment (excluding lymph node biopsy) within the past 14 days, or those who are expected to undergo large-scale surgical treatment during the treatment process;
* 13\. There are other serious physical or mental illnesses or laboratory abnormalities that may increase the risk of participating in the study, or interfere with the study results, as well as patients deemed unsuitable by the researchers to participate in this study.

主要终点：1-year progression free survival rate (1-year-PFSR) · The 1-year progression-free survival rate (1-year PFSR) is defined as the proportion of patients who are alive and progression-free at 1 year after CAR-T cell infusion. · 2 year after treatment
次要终点：overall survival (OS)；progression free survival (PFS)；disease free survival (DFS)；duration of response (DOR)；event free survival (EFS)；recurrence rate；Number of participants with treatment-related adverse events as assessed by CTCAE v5.0

• CD22/CD19 CAR-T cell immunotherapy · EXPERIMENTAL · patients with high-risk invasive Follicular Lymphoma who accept targeted CD22/CD19 CAR-T cell immunotherapy for first-line consolidation therapy

The purpose of this study is to determine the efficacy and safety of CD19/CD22 Chimeric Antigen Receptor (CAR) T-Cell immunotherapy as first-line consolidation therapy in patients with follicular lymphoma.