JY231 Injection in the Treatment of Relapsed or Refractory B-cell Lymphoma

Inclusion Criteria:

1. understand and sign the informed consent and are willing and able to comply with alltest requirements;
2. Age 18-75 years old, gender is not limited;
3. Flow cytometry or malignant tumor cells were CD19 positive;
4. Meet the clinical criteria for r/r B-cell lymphoma, including: indolent lymphoma (iNHL), follicular lymphoma (FL) and marginal zone lymphoma (MZL); Invasive B-celllymphoma, including diffuse large B-cell lymphoma (DLBCL), primary mediastinal largeB-cell lymphoma (PMBCL), transformed follicular lymphoma (TFL), and T-lymphocyt-richlarge B-cell lymphoma (TCRBCL);
5. There is at least one measurable lesion on imaging (Lugano 2014 criteria), that is, alymph node lesion with a diameter greater than 15 mm on CT cross-sectional images oran extranodal lesion with a diameter greater than 10 mm, with a positive FDG-PET test.
6. Expected survival ≥12 weeks;
7. The ECOG (Eastern Tumor Collaboration Group) score at baseline was 0 ~ 1;
8. Adequate organ function (indicators involving liver and kidney function can beappropriately relaxed) :

• ALT ≤3 xULN;
• AST)≤3x ULN;
• Total bilirubin ≤1.5 x ULN;
• Serum creatinine ≤ 1.5x ULN, or creatinine clearance ≥60 mL/min;
• Indoor oxygen saturation ≥92%;
• Left ventricular ejection fraction (LVEF) ≥55%, echocardiography confirmed nopericardial effusion, no clinically significant ECG findings;
• No clinically significant pleural effusion;

9. Sufficient who with adequate bone marrow reserve, defined as: Absolute neutrophil count (ANC) > 1.000 /mm3; Absolute lymphocyte count (ALC) ≥300 /mm3; Platelet ≥50.000 /mm3; Hemoglobin > 8.0g/dl;
10. Using the following drugs must meet the following conditions:

• Steroids: Therapeutic doses of steroids must be discontinued 72 hours beforeJY231 infusion. Physiological replacement doses of steroids are permitted;
• Immunosuppression: Any immunosuppressive drug must be stopped ≥4 weeks prior toenrollment;
• Anti-proliferative therapy other than lympho-depleting chemotherapy within twoweeks of infusion; CD20 antibody therapy must be discontinued within 4 weeksprior to infusion or 5 half-lives (whichever is older);
• CNS disease prevention must be stopped 1 week before JY231 infusion (e.g.,intrathecal methotrexate).

11. Fertile men, to ensure that sexual partners can effectively prevent contraception;Women who are fertile, use effective birth control and consent to use birth controlthroughout the study period.

Exclusion Criteria:

1. Subjects with active cerebrospinal fluid malignant cells or brain metastases, orsubjects with active central nervous system (CNS) lymphoma;
2. Subjects with a history of active CNS disease, such as seizures, cerebrovascularischemia/bleeding, dementia, cerebellar disease, or any autoimmune disease involvingthe central nervous system;
3. Subjects who have received other study drugs within 30 days prior to screening;
4. Subjects who have previously received any anti-CD19 / anti-CD3 therapy or any otheranti-CD19 therapy (except those with adequate bone marrow reserve and whose tumor isCD19-positive);
5. Patients who have previously been treated with any gene therapy product, includingCAR-T therapy (except those with no CAR T in the body, normal T cell count andfunction, and CD19-positive tumors);
6. Subjects undergoing radiation therapy within 2 weeks prior to infusion;
7. Subjects with active hepatitis B (defined as hepatitis B virus DNA test value > 500IU/mL) or hepatitis C (HCV RNA positive); Hiv-positive or treponem-positive subjects;
8. Subjects with an acute life-threatening bacterial, viral, or fungal infection that hasnot yet been controlled (e.g., positive blood culture ≤72 hours prior to infusion);
9. Participants with unstable angina pectoris and/or myocardial infarction in the 6months prior to screening;
10. Subjects with prior or concurrent development of other malignancies, except in thefollowing cases:

• Adequately treated basal cell, thyroid papillary, squamous cell carcinomas (requiring adequate wound healing prior to enrollment);
• Carcinoma in situ of cervical or breast cancer with curative treatment and nosigns of recurrence for at least 3 years prior to the study;
• The primary malignancy has been completely removed and in complete remission for ≥5 years.

11. Clinically significant ventricular arrhythmia;
12. Subjects received anticoagulant therapy within a week;
13. Active neuroautoimmune or inflammatory conditions (e.g. Guillian-Barre syndrome,amyotrophic lateral sclerosis);
14. Pregnant or lactating women, and female subjects who are planning to become pregnantwithin 2 years after JY231 injection infusion or male subjects whose partners plan tobecome pregnant within 2 years after JY231 injection infusion;
15. Subjects who, in accordance with the investigator's judgment and/or clinicalstandards, are contraindicated with any study procedure or have other medicalconditions that may place them at unacceptable risk.
16. Other conditions that the investigator believes should not be included in thisclinical trial, such as poor compliance.