Clinical Study of Combined EphA2-targeted CAR-DC and CAR-T Cell Therapy for Non-small Cell Lung Cancer

Inclusion Criteria:

1. Pathologically confirmed stage IV non-small cell lung cancer (NSCLC) with at least one measurable lesion according to RECIST 1.1 criteria (i.e., a lesion with the longest diameter ≥10 mm on spiral CT scan or a lymph node with a short axis ≥15 mm).
2. Tumor tissue tested positive for EphA2 expression by immunohistochemistry (≥20%).
3. Disease progression after standard treatment or no available standard treatment (patients must have received at least two prior systemic therapies, including but not limited to chemotherapy and immune checkpoint inhibitors; patients with actionable driver mutations must have failed targeted therapy).
4. ECOG performance status: 0-1.
5. Expected survival ≥6 months.
6. Toxicities related to prior anti-tumor treatments must have resolved to baseline levels or ≤ Grade 1 (excluding residual alopecia); Grade ≤2 neurotoxicity is acceptable. Washout periods: 4 weeks for chemotherapy and immunotherapy, 2 weeks for targeted therapy.
7. Adequate organ function, including:

   * Adequate hematologic function: Absolute neutrophil count (ANC) ≥1.5×10\^9/L, platelet count ≥75×10\^9/L, hemoglobin ≥9 g/dL. No transfusions, granulocyte colony-stimulating factor (G-CSF), thrombopoietin, or erythropoietin allowed within 14 days before blood tests.
   * Adequate hepatic function: Total bilirubin (TBIL) \<1.5× upper limit of normal (ULN); AST and ALT \<2.5×ULN. For patients with Gilbert's syndrome, TBIL \<2×ULN; if liver metastases are present, AST and ALT \<5×ULN.
   * Adequate renal function: Serum creatinine (Cr) ≤1.5×ULN, or if Cr \>1.5×ULN, creatinine clearance (CrCl) ≥60 mL/min calculated using the Cockcroft-Gault formula.
   * Adequate coagulation function: Prothrombin time (PT) and activated partial thromboplastin time (APTT) \<1.5×ULN; international normalized ratio (INR) \<1.5 or within the target range if on anticoagulant therapy.
8. Subjects of reproductive potential must be willing to use effective contraception.
9. Ability to understand and voluntarily sign the informed consent form.
10. Willingness to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures.

Exclusion Criteria:

1. Pathologically confirmed mixed histology, such as adenosquamous carcinoma of the lung.
2. Tumor-related emergencies requiring urgent treatment, such as malignant pericardial effusion or cardiac tamponade, superior vena cava syndrome, or spinal cord compression.
3. Significant cardiovascular diseases, including:

   * Documented cardiovascular events within the past 6 months, such as myocardial infarction, angina, heart failure, severe arrhythmia, or having undergone angioplasty, stent implantation, or coronary artery bypass surgery.
   * Clinically significant QT/QTcF prolongation (QT/QTcF \> 470 ms in females or \> 450 ms in males).
4. Clinically significant bleeding tendency or coagulation disorders, such as hemophilia.
5. HIV or syphilis infection; active hepatitis B or C:

   * Hepatitis B: HBV-DNA ≥ 1000 IU/mL.
   * Hepatitis C: Positive HCV RNA with abnormal liver function.
6. History of involuntary commitment due to psychiatric disorders or other psychological conditions deemed unsuitable for treatment by the investigator.
7. Presence of other autoimmune diseases, or long-term use of immunosuppressive agents or corticosteroids.
8. Poor medication compliance.
9. Any other condition that the investigator considers grounds for exclusion.