Effect of NK Cell Immunotherapy on Advanced Lung Adenocarcinoma Adenocarcinoma With EGFR Mutation

Study Overview
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Brief Summary
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This study was attempted to investigate the efficiency of NK cells immunotherapy on non-small cell lung cancer with and without EGFR mutation, and evaluated response rate (RR) and the progression-free survival (PFS).

Detailed Description
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Investigators will enrolle 100 patients who met the enrollment criteria. 50 patients were clinically confirmed EGFR mutation positive. They were divided into two groups (group A and group C according to if accepted NK therapy) in accordance with the principles of randomized. The rest 50 patients which were EGFR mutation negative were also divided into two groups (group B and group D) in accordance with the principles of randomized to be paired respectively with group A and group C. Comparison of lymphocyte number, serum tumor related biomarkers, circulating Tumor Cell (CTC), KPS and survival curves was carried out before after NK cell immunotherapy. The safety and short-term effects were evaluated followed by the median PDA, response rate assessment.

Official Title
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Effect of Autologous NK Cell Immunotherapy on Advanced Lung Adenocarcinoma With EGFR Mutation: a Preliminary Clinical Study

Conditions
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NK Cell Mediated Immunity

Intervention / Treatment
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* Biological: NK cells


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The criteriaof the enrollment are as following: (1) expected survival>6 months; (2) age between35-75 years old; (3) KPS >45; (4) platelets>80 × 109/L, WBC>3 × 109/L, hemoglobin>90g/L, prothrombin time-international normalized ratio (0.8-1.5), adequate hepatic function (bilirubin < 20 μM, aminotransferase<60 U/L) and renal function (serum creatinine < 130 μM, serum urea <10 mM); (5) All patients confirmed by pathology and/or imaging; Exclusion Criteria: The absence of level 3 hypertension, severe coronary disease, myelosuppression, respiratory disease, acute or chronic infection, and autoimmune diseases. -

Ages Eligible for Study
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Minimum Age: 35 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: EGFR+NK+<br>The EGFR mutation positive patients were with the principles of randomized and NK cells treatment. | Biological: NK cells<br>* NK cells were generated in good manufacturing practice (GMP) condition. In brief, PBMCs were isolated from 50mL patient's blood with Ficoll-Hypaque(Morecell Biomedical Co. Ltd., Shenzhen, China). Then the Human NK Cell Culture Kit (Cat. No. MCF-004, Morecell Biomedical Co. Ltd., Shenzhen, China) and Serum-free Medium for NK Cells (MCM-002, Morecell Biomedical Co. Ltd., Shenzhen, China) was used for induction of NK cells according to the manufacturer's instructions. Three days before NK cell transfusion, the NK cells were sampled and sent to detect the NK cell quality.<br>* Other names: randomized;|
| No Intervention: EGFR+NK-<br>The EGFR mutation positive patients were with the principles of randomized and without NK cells treatment . | |
| Experimental: EGFR-NK+<br>The EGFR mutation negative patients were with the principles of randomized and NK cells treatment . | Biological: NK cells<br>* NK cells were generated in good manufacturing practice (GMP) condition. In brief, PBMCs were isolated from 50mL patient's blood with Ficoll-Hypaque(Morecell Biomedical Co. Ltd., Shenzhen, China). Then the Human NK Cell Culture Kit (Cat. No. MCF-004, Morecell Biomedical Co. Ltd., Shenzhen, China) and Serum-free Medium for NK Cells (MCM-002, Morecell Biomedical Co. Ltd., Shenzhen, China) was used for induction of NK cells according to the manufacturer's instructions. Three days before NK cell transfusion, the NK cells were sampled and sent to detect the NK cell quality.<br>* Other names: randomized;|
| No Intervention: EGFR-NK-<br>The EGFR mutation negative patients were with the principles of randomized and without NK cells treatment. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical response | Based on the Response Evaluation Criteria Solid Tumors (RECIST), the therapeutic effect was divided into complete response (CR), partial response (PR),stable disease (SD), progressive disease (PD). Investigators calculated the sum area of all tumors 3 months after NK treatment. The recent curative effect must have been maintainedat >4 weeks; CR + PR denoted the effective response rate (RR). | Calculated the sum area of all tumors 3 months after NK treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Detection of immune function | Patients were detected Lymphocyte subgroups of 1ml peripheral blood by Flow cytometer (BD FACSCalibur), which inclunde the T cell number, CD4T cell number, CD8 T cell number and NK cell number. | Before and 3 months after NK cell therapy | 
| Analysis of tumor biomarker CEA and CA125 levels in serum | Patients were detected the Serum Carcinoembryonic antigen (CEA) and CA125 level by Elisa kit.Investigators compared the level of CEA and CA125 in serum before and 3 months after NK cell therapy to perform the therapeutic evaluation. factor to identify patients tumor recurrence.We then compared the level of CEA and CA125 in serum before and 3 months after NK cell therapy to perform the therapeutic evaluation. | Before and 3 months after NK cell therapy |