Study of CXCR5 Modified EGFE Chimeric Antigen Receptor Autologous T Cells in EGFR- Positive Patients With Advanced Non-small Cell Lung Cancer

This is an interventional treatment trial for Non Small Cell Lung Cancer focused on measuring EGFR, CAR-T cells, NSCLC Read More

Inclusion Criteria:

• All subjects or legal guardians must sign the informed consent form approved by the ethics committee in writing before starting any screening procedure;
• 18 Years to 75 Years, Histologically or cytologically confirmed Routine treatment of patients with advanced non-small cell lung cancer;
• 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;
• Pathological results suggest that CXCL13 factor positive rate ≥ 10 %;
• 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);
• Expected survival time ≥ 12 weeks;
• The Eastern oncology group strength status score (ECOG) was 0-1;
• 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;
• The hemodynamics determined by echocardiography or multichannel radionuclide angiography(MUGA) are stable and the left ventricular ejection fraction (LVEF)≥50%;
• 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;
• 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.

• 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:

• Patients who have previously received any gene therapy product treatment, including CAR-T treatment;
• 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;
• Patients with severe liver and kidney dysfunction or consciousness disorders;
• Patients who had undergone chemotherapy other than lymphocyte clearance chemotherapy within 14 days before the EGFR CAR-T infusion;
• Screening of patients who had received other research drugs within 30 days before;
• Patients undergoing radiotherapy within 2 weeks before infusion;
• Patients with active hepatitis B: HBVDNA >1000 cps/ml;
• Patients with HIV antibody, hepatitis C antibody, syphilis spirocyte positive；
• Patients with The sputum smear and tuberculosis infection T cell test positive;
• Patients with Interstitial lung disease or pneumonia;
• 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);
• 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;
• 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.

• Pregnant or lactating women;
• Patients with history of T cell tumors or present with the disease.
• Having autoimmune or inflammatory disorders of active nerves (such as Guillian-Barre syndrome, amyotrophic lateral sclerosis);
• The researchers believe that other circumstances such as compliance should not be involved in this clinical trial.