Study of CXCR5 Modified EGFR Targeted CAR-T Cells for Advanced NSCLC

Inclusion Criteria:

1. All subjects or legal guardians must sign the informed consent form approved by the ethics committee in writing before starting any screening procedure;
2. 18 Years to 75 Years, Histologically or cytologically confirmed Routine treatment of patients with advanced non-small cell lung cancer(Including TKI treatment failure patients);
3. After the signature of the informed consent and prior to the collection of a single nuclear cell, the immuno- histochemical test must determine that the expression of EGFR in the tumor site of the patient reaches the positive standard and the score is 2 + or more;
4. Pathological results suggest that CXCL13 factor positive rate ≥ 10 %;
5. According to RECIST 1.1. The patient has at least one tumor lesion that can be measured (Results available within one month prior to screening period);
6. Expected survival time ≥ 12 weeks;
7. The Eastern oncology group strength status score (ECOG) was 0-1;
8. Patients must have evidence of adequate hepatic and renal function as evidenced by the following laboratory parameters: Serum creatinine≤ 1.6 mg/ml or the creatinine clearance ≥ 40 ml/min/1.73m. Total bilirubin \< 1.5 times upper limits of normal;
9. The hemodynamics determined by echocardiography or multichannel radionuclide angiography(MUGA) are stable and the left ventricular ejection fraction (LVEF)≥50%;
10. Have sufficient bone marrow reserves (subjects can meet this requirement through blood transfusion), defined as: The number of white blood cells should not be less than 2 × 10\^9/L;Platelet≥100 x 10\^9/L; Hemoglobin ≥100 g/L;
11. If the patient uses the following drugs, the following conditions must be met:

    Glucocorticoid: The therapeutic dose of glucocorticoid must be stopped 2 weeks before the EGFR CAR-T infusion. However, the following physiological replacement doses of glucocorticoids are allowed: 12 mg/m2 / dihydrogenated cortisone or equivalent; Immunosuppressive drugs: any immunosuppressive drugs must be stopped before they are selected for 4 weeks; Stop using granulocyte colony factor a week before plasmaphoresis.
12. Women of childbearing age and all male subjects must agree to use effective contraceptive methods for at least 52 weeks after EGFR CAR-T infusion, and until two consecutive PCR tests show that CAR-T cells are no longer present in the body.

Exclusion Criteria:

1. Patients who have previously received any gene therapy product treatment, including CAR-T treatment;
2. Patients with uncontrolled hypertension (\> 160/95), unstable coronary artery disease confirmed by uncontrolled arrhythmias, unstable angina, decompensated congestive heart failure(\>New York Heart Association Class II) or myocardial infarction within 6 months before cell infusion;
3. Patients with severe liver and kidney dysfunction or consciousness disorders;
4. Patients who had undergone antitumor chemotherapy other than lymphocyte clearance chemotherapy within 14 days before the EGFR CAR-T infusion;
5. Screening of patients who had received other research drugs within 30 days before infusion;
6. Patients undergoing radiotherapy and TKI treatment within 2 weeks before infusion ;
7. Patients with active hepatitis B: HBVDNA \>1000 cps/ml;
8. Patients with HIV antibody, hepatitis C antibody, syphilis spirocyte positive；
9. Patients with The sputum smear and tuberculosis infection T cell test positive;
10. Patients with Interstitial lung disease or pneumonia;
11. Patients with acute life-threatening bacteria, viruses or fungal infections that have not yet been controlled(for example, before transfusion ≤ 72 hours of blood culture positive);
12. Patients with central nervous system metastasis (after cerebral metastasis treatment is stable for more than 4 weeks and patients with asymptomatic brain metastasis do not need treatment), pericardial metastasis accompanied by a large amount of pericardial effusion;
13. Patients with a previous or concurrent second tumor, with the following exceptions:

    Adequate treatment of basal or squamous cell carcinoma(adequate wound healing prior to entry into the study);In situ cancer of the cervix or breast cancer with no signs of recurrence at least three years prior to the study following curable treatment; The primary malignant tumor has been completely removed and has been completely relieved for 5 years.
14. Pregnant or lactating women;
15. Patients with history of T cell tumors or present with the disease.
16. Having autoimmune or inflammatory disorders of active nerves (such as Guillian-Barre syndrome, amyotrophic lateral sclerosis);
17. The researchers believe that other circumstances such as compliance should not be involved in this clinical trial.