Phase I Study of Umbilical Cord Blood Natural Killer (NK) Cell Therapy for Children With High-risk, R/R Neuroblastoma.

Inclusion Criteria:

All of the following criteria must be met in order to be eligible for this trial:

1. Agree to participate in the trial and sign a written informed consent form;

2. Age ≤18 years, gender not limited;

3. Karnofsky (≥16 years old) or Lansky (<16 years old) physical status score (AppendixII) of at least 50;

4. Patients diagnosed with high-risk, recurrent/refractory neuroblastoma in childrenaccording to clinical diagnostic criteria, who have undergone comprehensivetreatment (surgery, chemotherapy, radiotherapy ± stem cell transplantation ± GD2monoclonal antibody therapy);

5. Expected survival period of at least 12 weeks;

6. The patient must have fully recovered from the acute toxic effects of all previousanticancer chemotherapy, such as recovery to grade I after bone marrow suppression;

7. Bone marrow suppressive chemotherapy: At least 21 days after the last bone marrowsuppressive chemotherapy (if nitrosoureas were used previously, then 42 days);

8. Investigational drugs or anticancer therapies other than chemotherapy: Must not beused within 28 days before the planned start of NK cell immunotherapy. Full recoveryfrom the clinically significant toxicity of that therapy must be confirmed;

9. Hematopoietic growth factors: At least 14 days after the last dose of long-actinggrowth factors or 3 days after the last dose of short-acting growth factors;

10. X-ray therapy (XRT): At least 14 days after local palliative XRT (small field port);if other substantial bone marrow (BM) irradiation is involved, including priorradioactive iodine metaiodobenzylguanidine (131I-MIBG) treatment, it must end atleast 42 days ago;

11. Stem cell infusion without total body irradiation (TBI): No active graft-versus-hostdisease, must have ended at least 56 days after transplantation or stem cellinfusion;

12. Laboratory tests during the screening period must meet the following conditions:

13. Absolute neutrophil count (ANC) ≥1.0×10^9/L (if bone marrow involvement, thenANC ≥0.5×10^9/L)

14. Platelet count (PLT) ≥75×10^9/L (if bone marrow involvement, then PLT ≥20×10^9/L)

15. Bilirubin ≤1.5 times the upper limit of normal (ULN)

16. Creatinine ≤1.5 times ULN (calculated using the standard Cockcroft-Gaultformula)

17. ALT/AST ≤3 times ULN (if there is liver metastasis, this can be relaxed to 5times ULN)

18. During the study period, able to comply with outpatient treatment, laboratorymonitoring, and necessary clinical visits; parents/guardians of pediatric oradolescent participants are capable of understanding, consenting to, and signing theinformed consent form (ICF) and applicable child assent forms before initiating anyprotocol-related procedures; with parental/guardian consent, the participant iscapable of expressing their consent (when applicable).

Exclusion Criteria:

Patients who meet any of the following criteria are not eligible for this trial:

1. Symptomatic brain metastases (patients whose brain metastases have been treated andwhose symptoms have been stable for more than two months prior to enrollment may beenrolled, but must be confirmed by cranial MRI, CT, or venography as having nosymptoms of cerebral hemorrhage);

2. Suffering from the following cardiovascular diseases: grade II or higher myocardialischemia or myocardial infarction, poorly controlled arrhythmias (including QTcinterval ≥450 ms for males and ≥470 ms for females); according to the NYHA standard (Appendix Three), class III-IV heart failure, or echocardiography indicating leftventricular ejection fraction (LVEF) <50%;

3. Having a history of interstitial lung disease or suffering from interstitial lungdisease at the same time;

4. Coagulation disorders (INR >1.5 or prothrombin time (PT) >ULN +4 seconds or APTT >1.5 ULN), with a tendency to bleed or currently receiving thrombolytic oranticoagulant therapy;

5. Arterial/venous thromboembolic events occurring within 12 months before enrollment,such as cerebrovascular accidents (including transient ischemic attacks, cerebralhemorrhage, cerebral infarction), deep vein thrombosis, and pulmonary embolism;

6. Known hereditary or acquired bleeding and thrombosis tendencies (such as hemophiliapatients, coagulation disorders, thrombocytopenia, splenomegaly, etc.);

7. Long-term unhealed wounds or fractures (except pathological fractures caused bytumors);

8. Receiving major surgery or experiencing severe traumatic injuries, fractures, orulcers within 4 weeks before enrollment;

9. Factors significantly affecting the absorption of oral medications, such asinability to swallow, chronic diarrhea, and intestinal obstruction;

10. Experiencing abdominal fistula, gastrointestinal perforation, or abdominal abscesswithin 6 months before enrollment;

11. Routine urine tests showing proteinuria ≥ +, and confirmed 24-hour urine proteinquantification ≥1.0 g;

12. Symptomatic serosal effusions requiring symptomatic treatment (including pleuraleffusion, ascites, pericardial effusion); Note: Asymptomatic serosal effusions canbe enrolled, symptomatic serosal effusions after active symptomatic treatment (anticancer drugs cannot be used for treating serosal effusions), judged by theinvestigator to meet the enrollment criteria can be enrolled;

13. Active infections requiring antimicrobial treatment (e.g., needing antibacterialdrugs, antiviral drugs, excluding chronic hepatitis B antiviral treatment,antifungal drug treatment);

14. History of psychoactive substance abuse that cannot be quit or has mental disorders;

15. Participated in other antitumor drug clinical trials within 4 weeks beforeenrollment;

16. Receiving systemic hormone therapy or undergoing any form of immunosuppressivetherapy within 2 weeks before the first administration;

17. In the past 2 years, suffered from active autoimmune diseases requiring systemictreatment (such as using disease-modifying drugs, corticosteroids, orimmunosuppressants); Note: Substitutive treatments (such as thyroxine, insulin, orphysiological corticosteroid replacement therapy for adrenal or pituitaryinsufficiency) do not count as systemic treatment;

18. Contraindications for IL-2 use;

19. Suffering from active infections requiring intravenous systemic treatment;

20. Vaccinated with live vaccines within one month before the first use of the studydrug, seasonal influenza vaccination with inactivated virus vaccines is allowed, butintranasal attenuated live influenza vaccines are not allowed;

21. Previous or concomitant other uncured malignancies, cured skin basal cell carcinoma,cervical carcinoma in situ, and superficial bladder cancer are excluded;

22. Other conditions judged by the investigator that may affect the conduct of theclinical study and the determination of study results;

23. Virological tests during the screening period show any of the following:

24. HBsAg positive and HBV DNA exceeds the upper limit of normal

25. Anti-HCV positive and HCV RNA positive

26. HIV positive

27. Undergone allogeneic tissue/organ transplantation;

28. Poor compliance, unable to cooperate with the clinical study.