复发/难治性血液系统肿瘤的精准细胞治疗设计研究

Inclusion Criteria:

Patients with relapsed/refractory hematologic malignancies confirmed to express CD19, CD22, CD20, CD7, CD5, CD2, CD79b, BCMA, GPCR5D, CD38, CD33, CD123, CD133, CLL1, EBV (GP350, LMP1), CMV (Gb21, gB280…) or other validated targets (supported by domestic and international preclinical/clinical evidence) who meet the following criteria:

Male or female, aged ≥18 years and \<75 years; Newly diagnosed patients with refractory disease (as defined by respective diagnostic criteria) after chemotherapy; Newly diagnosed patients with disease progression during chemotherapy and poor anticipated response to further chemotherapy; Patients with relapsed disease (≥1 recurrence) and confirmed residual tumor evidence; Patients with relapse after autologous or allogeneic hematopoietic stem cell transplantation (HSCT); Patients with relapse after CAR-T therapy; Patients with hematologic malignancies deemed incurable by current surgical, radiotherapy, or chemotherapy interventions.

Exclusion Criteria:

Patients meeting any of the following criteria will be excluded:

Life expectancy \<12 weeks; Genetic testing reveals mutations or structural variants associated with the target antigens; Severe graft-versus-host disease (GVHD) requiring immunosuppressive therapy in post-HSCT relapse patients; Post-HSCT relapse \<3 months with no available donor;

Organ dysfunction:

Serum creatinine \>2.5 mg/dL; ALT/AST \>5× upper limit of normal (ULN); Total bilirubin \>2 mg/dL; Uncontrolled active infection; Active hepatitis B/C or HIV infection; Anticipated early loss to follow-up (\<3 months post-treatment); Failure to provide signed informed consent or lack of ethics committee approval; Concurrent systemic conditions that may interfere with study participation; Other exclusion criteria deemed appropriate by the investigator.

主要终点：adverse events. · Type, incidence and severity of adverse events · 1 month；Maximum tolerated dose · The maximum dose that does not cause death of the subject · 1 month；Overall response rate · ORR in patients is defined as the rate of complete remission (CR, CRh) · 3 months
次要终点：Overall incidence and severity of adverse events.；Rate of relapse and refractory of Hematologic Diseases patients achieving MRD negative CR

• Precise Design of CAR-cell Injection · EXPERIMENTAL · The drug for this trial is Precise Designof CAR- cells transduced with the lentiviral vector . The dose is 2x10e6 \~1x10e7 CAR-cell/kg in patients with relapsed/refractory hematologic malignancies.

This clinical trial aims to evaluate the efficacy and safety of CAR-T cell therapy in patients with relapsed/refractory hematologic malignancies.