Natural Killer(NK) Cell Combined With Programmed Death-1(PD-1) Antibody as Second Line Therapy for Advanced Driver Mutation Negative Non-small Cell Lung Cancer

Inclusion Criteria:

* (1) Age ≥ 18 years old.
* (2) Locally advanced (IIIB/IIIC phase) or metastatic NSCLC (squamous or non-squamous) confirmed by histological examination.
* (3) Disease progression occurred after platinum-based chemotherapy in the previous line, and measurable lesions existed according to RECIST v1.1.
* (4) Patients must be able to provide fresh or archived tumor tissue and pathology reports. Non-squamous NSCLC must be able to provide a report that is confirmed to be wild-type EGFR by tissue-based assays.
* (5) Eastern Cooperative Oncology Group(ECOG) performance status(PS) ≤ 1.
* (6) The vital organs are fully functional, and the following results are obtained for each laboratory indicator (accepting the results of the examinations made within ≤ 28 days before randomization):

  * Cardiac ultrasound indicates a cardiac ejection fraction ≥ 50%; blood oxygen saturation ≥ 90%;
  * Absolute neutral cell count (ANC) ≥ 1.5 x 109/L, platelet count ≥ 100 x 109/L, hemoglobin ≥ 90g/dL;
  * Creatinine (Cr) ≤ 2.5 times normal range;
  * Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 times normal range, total bilirubin (TBIL) ≤ 1.5 times normal range.
* (7) No contraindications for apheresis and cell separation.
* (8) Male or female with fertility needs to agree to take effective contraceptive measures during the study period and at least 120 days after the end of medication.
* (9) A written informed consent can be provided and the research requirements are understood and followed.

Exclusion Criteria:

* (1) Previously received immunological checkpoint inhibitors targeting PD-1, PD-L1 or C ytotoxic T - L ymphocyte A ntigen 4(CTLA-4) and other immunotherapies (including but not limited to interferon or IL-2, chimeric antigen receptor T Cells, vaccines, etc.).
* (2) NSCLC with EGFR gene mutation or ALK gene translocation.
* (3) The toxicity caused by previous anticancer treatment has not recovered to baseline level or returned to stability (except for hair loss, rash, pigmentation or specific laboratory abnormalities).
* (4) A history of severe allergic reactions to other monoclonal antibodies.
* (5) History of interstitial pneumonia, non-infectious pneumonia or uncontrolled systemic diseases, including diabetes, hypertension, and pulmonary fibrosis.
* (6) Clinically severe pericardial effusion.
* (7) Pleural effusion or ascites that is clinically uncontrolled and requires thoracentesis or abdominal puncture drainage within 2 weeks prior to randomization.
* (8) Active pia mater disease or unstable brain metastasis.
* (9) Major surgery, open biopsy or severe traumatic injury was performed ≤ 28 days prior to randomization, or major surgical procedures were expected during the study.
* (10) Other malignant tumors other than NSCLC (except for surgically resected non-melanoma skin cancer, fully treated cervical carcinoma in situ, cured local prostate cancer, fully treated low-grade bladder cancer, Curatively treated breast ductal carcinoma in situ, or a malignant tumor diagnosed 2 years ago, but there is currently no evidence of disease in the absence of treatment ≤ 2 years prior to randomization).
* (11) Severe chronic or active infections requiring systemic antibacterial, antifungal or antiviral treatment, including HIV, hepatitis B virus(HBV), hepatitis C virus(HCV) infection.
* (12) Active autoimmune disease or a history of autoimmune disease but may recur.
* (13) Subjects who require systemic treatment with corticosteroids or other immunosuppressive agents within 14 days prior to randomization.
* (14) Those who have undergone organ transplantation or hematopoietic stem cell transplantation.
* (15) Any live vaccine against infectious diseases (eg, influenza, chickenpox, etc.) was used within 28 days prior to randomization.
* (16) Meet any of the following cardiovascular disease criteria:

  * Evidence of acute or positive myocardial ischemia
  * There are currently symptomatic pulmonary embolisms
  * Acute myocardial infarction occurred within ≤6 months before randomization.
  * Has reached the New York Heart Association grading standard (see Appendix 5) 3 or 4 before randomization ≤ 6 months Grade of heart failure.
  * A ≥2 grade ventricular arrhythmia occurred within ≤6 months before randomization.
  * A cerebrovascular accident (CVA) or transient ischemic attack (TIA) occurred within ≤6 months before randomization.
* (17) Pregnant and lactating women.
* (18) If the patient is unable to follow the study procedures, limitations, and requirements, the investigator believes that the patient is not allowed to participate in the study.