Chimeric Natural Killer Receptor-Universal T Cells for Relapsed or Refractory Neuroblastoma

Inclusion Criteria:

1. Aged 1-12 years with weight≥10kg, male or female;

2. The child and/or guardian has signed the informed consent form (ICF) and has theability to comply with the study requirements.

3. Diagnosed with relapsed/refractory neuroblastoma. Clinical diagnostic criteria andfirst-line standard treatment can refer to the NCCN guidelines:

4. Relapsed neuroblastoma: New lesions appear at the primary site or otherlocations 4 weeks after achieving complete remission through first-linestandard treatment.

5. Refractory neuroblastoma: Failure to achieve complete remission after standardtreatment protocols, which include induction chemotherapy, surgery, andradiotherapy targeting the primary tumor and residual metastatic sites;

6. Prior to enrollment, appropriate measures can be implemented to ensure that thesubject's disease status is either partial remission (PR) or stable disease (SD).

7. According to the INRC efficacy criteria, there must be at least one lesion whoseefficacy can be assessed through functional imaging (123I-MIBG) and/or bone marrowexamination (bone marrow aspiration or biopsy). If soft tissue lesions are present,the longest diameter of the target lesion should be ≤2 cm.

8. Tumor tissue sections or paraffin blocks can be provided, and it has been confirmedthrough immunohistochemistry (IHC) that the tumor tissue expresses B7-H3.

9. Lansky score>60；

10. Estimated life expectancy > 12 weeks;

11. Adequate organ and bone marrow function, and the laboratory test value meets thefollowing requirements within 7 days before enrollment, as follows:

(1)Blood Routine Test: Absolute neutrophil count(ANC)≥1.5×10^9/L;Absolute lymphocyte count (ALC)≥0.2×10^9/L；Platelet count ≥75×10^9/L; Haemoglobin≥90g/L; (2)Heart: Left ventricular ejection fraction (LVEF)≥50%;Cardiac function Grade I-II; (3)Pulmonary function: indoor oxygen saturation≥92%. (4)Hepatic function：Total bilirubin≤3×ULN; Aspartate aminotransferase (AST) or alanine aminotransferase (ALT)≤5×ULN; (5)Renal function: Serum creatinine≤2×ULN, or Creatinine clearance rate (CCR)≥60 mL/min (Cockroft-Gault formula); 10.All toxic responses originating from previous radiotherapy, chemotherapy, or other treatments (occurring within 4 weeks or 5 half-lives of anti-tumor drugs therapy [including but not limited to chemotherapy, targeted therapy, immunotherapy, Chinese herbal medicine]) have returned to NCI CTCAEV5.0 Grade≤1 (except for hair loss).

Exclusion Criteria:

1. Suffering from malignant tumors or diagnosed within 5 years before enrollment,excluding radical skin basal cell carcinoma, skin squamous cell carcinoma, thyroidcancer, breast cancer (ductal carcinoma in situ) and / or radical resection ofcarcinoma in situ.

2. Participants with symptomatic central nervous system (CNS) metastasis confirmed byimaging or pathological examination.

3. Participants with MIBG non-avid disease.

4. Participants with a history of organ transplantation（excluding stem celltransplantation）;

5. Participants with active autoimmune diseases requiring systemic treatment (such asthe use of disease-modifying drugs, corticosteroids, or immunosuppressants) areconsidered. The use of replacement therapies (such as thyroxine, insulin, orphysiological corticosteroids for adrenal or pituitary insufficiency) is permitted.A known history of primary immunodeficiency is also noted. For patients who onlytest positive for autoimmune antibodies, the presence of autoimmune disease must beconfirmed based on the investigator's judgment.

6. Uncontrolled or irreparable systemic diseases, metabolic disorders, or othernon-malignant organ diseases or cancer sequelae, which may lead to higher medicalrisks and/or uncertainties in survival assessment.

7. Active pulmonary tuberculosis (TB), who is receiving anti-tuberculosis treatment orhas received anti-tuberculosis treatment within 1 year before enrollment; humanimmunodeficiency virus (HIV) infection, known syphilis infection.

8. Severe infections that are either active or poorly controlled clinically within 4weeks prior to enrollment, including but not limited to hospitalization due toinfections, bacteremia, or severe pneumonia complications (excluding mild urinarytract infections and upper respiratory tract infections).

9. Received radiotherapy, chemotherapy (excluding lymphodepletion), molecular targetedtherapy, immune checkpoint inhibitors, or other anti-tumor treatments within 4 weeksor 5 half-lives (whichever is shorter) before cell infusion..

10. Participants who have undergone major surgery (craniotomy, thoracotomy, orlaparotomy) within 4 weeks prior to the initiation of the study, or have severeunhealed wounds, ulcers, or fractures.

11. Participants who have received treatment from other clinical trials within 4 weeksprior to the initiation of the study.

12. Participants who receive attenuated live vaccines within 4 weeks prior to theinitiation of the study.

13. Participants who have used any gene therapy products prior to cell infusion.

14. Allergic to components of CNK-UT injection.

15. Participants suffer from known mental or substance abuse disorders, which mayinterfere with their ability to comply with research requirements.

16. Participants considered by the investigator to have other potentiallylife-threatening serious complications that may interfere with the evaluation ofthis study..

17. Other situations that the participant is identified by the investigator asunsuitable to participate in the study.