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 theethics committee in writing before starting any screening procedure;

2. 18 Years to 75 Years, Histologically or cytologically confirmed Routine treatment ofpatients with advanced non-small cell lung cancer(Including TKI treatment failurepatients);

3. After the signature of the informed consent and prior to the collection of a singlenuclear cell, the immuno- histochemical test must determine that the expression ofEGFR 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 bemeasured (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 bythe following laboratory parameters: Serum creatinine≤ 1.6 mg/ml or the creatinineclearance ≥ 40 ml/min/1.73m. Total bilirubin < 1.5 times upper limits of normal;

9. The hemodynamics determined by echocardiography or multichannel radionuclideangiography(MUGA) are stable and the left ventricular ejection fraction (LVEF)≥50%;

10. Have sufficient bone marrow reserves (subjects can meet this requirement throughblood transfusion), defined as: The number of white blood cells should not be lessthan 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 weeksbefore the EGFR CAR-T infusion. However, the following physiological replacementdoses of glucocorticoids are allowed: 12 mg/m2 / dihydrogenated cortisone orequivalent; Immunosuppressive drugs: any immunosuppressive drugs must be stoppedbefore they are selected for 4 weeks; Stop using granulocyte colony factor a weekbefore plasmaphoresis.

12. Women of childbearing age and all male subjects must agree to use effectivecontraceptive methods for at least 52 weeks after EGFR CAR-T infusion, and until twoconsecutive 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, includingCAR-T treatment;

2. Patients with uncontrolled hypertension (> 160/95), unstable coronary artery diseaseconfirmed by uncontrolled arrhythmias, unstable angina, decompensated congestiveheart 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 clearancechemotherapy within 14 days before the EGFR CAR-T infusion;

5. Screening of patients who had received other research drugs within 30 days beforeinfusion;

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 thathave not yet been controlled(for example, before transfusion ≤ 72 hours of bloodculture positive);

12. Patients with central nervous system metastasis (after cerebral metastasis treatmentis stable for more than 4 weeks and patients with asymptomatic brain metastasis donot need treatment), pericardial metastasis accompanied by a large amount ofpericardial 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 priorto entry into the study);In situ cancer of the cervix or breast cancer with no signsof recurrence at least three years prior to the study following curable treatment;The primary malignant tumor has been completely removed and has been completelyrelieved 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-Barresyndrome, amyotrophic lateral sclerosis);

17. The researchers believe that other circumstances such as compliance should not beinvolved in this clinical trial.