Exploration of Circular RNA in B-cell Hematologic Malignancies

Inclusion Criteria:

1. Age ≥ 18 years, any gender.
2. Able to provide written informed consent.
3. Confirmed diagnosis of relapsed/refractory (R/R) CD19-positive B-cell malignancy, including:

   * Diffuse large B-cell lymphoma (DLBCL)
   * Follicular lymphoma (FL)
   * Mantle cell lymphoma (MCL)
   * Small lymphocytic lymphoma (SLL)/chronic lymphocytic leukemia (CLL)
   * Waldenström macroglobulinemia (WM)
   * Marginal zone lymphoma (MZL)
4. ECOG performance status 0 or 1.and have archival tumor biopsy tissue and pathology report from the most recent relapse, or at least one palpable superficial tumor lesion at screening, and agree to biopsy/resection before the first dose of IP for disease confirmation.
5. Disease refractory to or relapsed after ≥ 2 prior lines of standard therapy, including required agents per disease subtype (e.g., anti-CD20, BTK inhibitors, chemotherapy, or ASCT if applicable).
6. Measurable disease per Lugano 2014 or iwCLL 2018 criteria.
7. LVEF ≥ 40% by echocardiogram.
8. For patients with prior CD19-targeted therapy, confirmed CD19 positivity at screening.
9. Women of childbearing potential (WOCBP) must have a negative serum pregnancy test and agree to use effective contraception during the study and for 6 months after last treatment.
10. Male patients with female partners must agree to use condoms, and partners must use effective contraception, during the study and for 6 months after last treatment.

Exclusion Criteria:

1. Prior anticancer therapy-related toxicities unresolved to baseline or ≤ Grade 1 (alopecia and peripheral neuropathy excepted).
2. Central nervous system (CNS) involvement by lymphoma.
3. Need for urgent treatment due to tumor mass effect or spinal cord compression.
4. Known hypersensitivity to any component of IP, including mRNA/LNP-based products.
5. History of another primary malignancy within the past 3 years, except adequately treated basal cell carcinoma, squamous cell carcinoma, or cervical carcinoma in situ.
6. Active hepatitis B (HBsAg-positive with detectable HBV DNA) or hepatitis C (HCV RNA-positive) infection.
7. Active or prior HIV infection.
8. Uncontrolled active systemic infection requiring IV therapy within 1 week before dosing.
9. Active or history of acute/chronic GVHD.
10. Inadequate hematologic function (ANC \<1.0×10⁹/L, Hb \<70 g/L, PLT \<50×10⁹/L, lymphocytes ≤0.5×10⁹/L) or coagulation abnormalities (INR/APTT ≥1.5×ULN).
11. Hepatic impairment (ALT/AST \>2×ULN, or \>3×ULN with hepatic involvement; bilirubin \>2×ULN, unless Gilbert syndrome).
12. Renal impairment (CrCl \<50 mL/min by Cockcroft-Gault).
13. Uncontrolled ischemic heart disease, NYHA Class III-IV heart failure, or baseline QTcF ≥450 ms (male) / ≥470 ms (female).
14. Severe psychiatric disorder history.
15. Pregnancy or breastfeeding.
16. Received prohibited treatments within 4 weeks before dosing, including high-dose corticosteroids (\>20 mg prednisone equivalent daily), chemotherapy, immunosuppressive therapy, prior CAR-T or other gene/cell therapy, or T-cell engagers.
17. Participation in another clinical study with investigational therapy within 3 months before dosing, or prior participation in cell/gene therapy trials.
18. Planned radiotherapy within 6 weeks after screening (unless only non-irradiated PET-positive lesions remain eligible).
19. Planned allogeneic HSCT within 90 days after screening.
20. Significant comorbidities or unstable medical conditions deemed by the investigator to compromise safety or study compliance.