Clinical Trial of CD5-targeted CAR-NK Therapy for Relapse/Refractory T-Cell Hematologic Malignancies

Inclusion Criteria:

• 1.Gender and Age: No gender restriction; age 18-75 years (inclusive). 2.Diagnosis: Confirmed diagnosis of T-cell acute lymphoblastic leukemia (T-ALL) or T-cell lymphoma, including:

1. T-ALL Patients: Bone marrow morphology during screening shows ≥5% blasts/immaturelymphocytes and/or flow cytometry confirms minimal residual disease (MRD)+, andmeets any of the following:

2. Refractory to ≥2 cycles of standard induction chemotherapy (failure to achieveCR).

3. Relapsed within 12 months after achieving CR with first-line induction therapy.

4. Failure to achieve CR or relapse after ≥2 lines of chemotherapy.

5. Relapse after hematopoietic stem cell transplantation (HSCT).

6. T-cell Lymphoma Patients: Confirmed diagnosis of T-lymphoblastic lymphoma (T-LBL) orT-cell non-Hodgkin lymphoma (including but not limited to: peripheral T-celllymphoma, not otherwise specified (PTCL-NOS), angioimmunoblastic T-cell lymphoma (AITL), anaplastic large cell lymphoma (ALCL), extranodal NK/T-cell lymphoma (ENKL),T-cell prolymphocytic leukemia (T-PLL), adult T-cell leukemia/lymphoma (ATLL),mycosis fungoides/Sézary syndrome (MF/SS) stage IIB or higher), and meets both:

7. At least one bidimensionally measurable lesion per Lugano 2014 criteria: nodallesions >1.5 cm in long axis; extranodal lesions >1.0 cm in long axis.

8. Refractory to ≥2 lines of chemotherapy, primary resistance, or relapsepost-HSCT. 3.CD5 Positivity: Confirmed by flow cytometry (≥80% tumor cells express CD5with mean fluorescence intensity [MFI] equivalent to normal T cells; Dimdefined as MFI ≥1 log lower than normal T cells; partial positivity defined as 20-80% tumor cells expressing CD5) or immunohistochemistry (>30% tumor cellsexpress CD5). 4.ECOG Performance Status: 0-2 . 5.Life Expectancy: ≥12 weeks. 6.OrganFunction:

9. Cardiac: Left ventricular ejection fraction (LVEF) ≥50% by echocardiography; nosignificant ECG abnormalities.

10. Renal: Serum creatinine ≤2.0×ULN.

11. Hepatic: ALT/AST ≤3.0×ULN (≤5.0×ULN if liver involvement); total bilirubin ≤2.0×ULN.

12. Pulmonary: Oxygen saturation ≥92% (room air). 7.No Contraindications: Toleukapheresis, venipuncture, or cell collection. 8.No Severe PsychiatricDisorders. 9.Contraception: Agreement to use effective contraception frominformed consent until 1 year post-CAR-NK infusion (for patients ofchildbearing potential). 10.Informed Consent: Signed by the patient or legal guardian, confirmingunderstanding of the trial's purpose and procedures.

Exclusion Criteria:

1. Prior CAR-NK therapy or genetically modified cell therapy.

2. Active CNS involvement at screening (prior CNS involvement with resolved statuspost-treatment is allowed).

3. Recent Anticancer Therapy:

4. Chemotherapy, targeted therapy, or investigational drugs within 2 weeks or 5half-lives prior to screening.

5. Radiotherapy within 2 weeks prior to screening.

6. Active/Uncontrolled Infection: Within 1 week prior to screening.

7. Cerebrovascular Event or Seizure: Within 6 months prior to screening.

8. Viral Infections:

9. HBV DNA > ULN (if HBsAg+ or HBcAb+).

10. HCV RNA > ULN (if HCV Ab+).

11. HIV+, syphilis+, or active tuberculosis.

12. Cardiac Disease:

13. NYHA Class III/IV congestive heart failure.

14. Myocardial infarction or CABG ≤6 months prior.

15. Clinically significant ventricular arrhythmia or unexplained syncope (excludingvasovagal/dehydration-related).

16. Severe cardiomyopathy.

17. Active/Uncontrolled Autoimmune Disease.

18. Prior Malignancy: Within 5 years, except for cured cervical carcinoma in situ,basal/squamous skin cancer, localized prostate cancer, or ductal carcinoma in situ.

19. Live Vaccination: Within 4 weeks prior to screening.

20. Pregnancy/Lactation: Pregnant, breastfeeding, or planning pregnancy within 1 yearpost-CAR-NK infusion.

21. Other: Investigator-determined ineligibility.