Phase I Trial of CEA Specific AAV-DC-CTL Treatment in Stage IV Gastric Cancer

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the clinical safety and preliminary efficacy of CEA specific cytotoxic T lymphocytes induced by dendritic cells infected by recombinant adeno-associated virus with CEA gene in the treatment of stage IV gastric cancer patients.

Detailed Description
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Carcinoembryonic antigen (CEA) describes a set of highly related glycoproteins involved in cell adhesion.CEA is normally produced in gastrointestinal tissue during fetal development, but the production stops before birth. The serum levels are raised in some types of cancer,such as Gastric Cancer.The expression of CEA in these cancers and succedent unfavourable prognosis such as tumor hyperplasia, recurrence make CEA become the desirable therapeutic target. Cancer immunotherapy is the use of the immune system to treat cancer. Immunotherapies fall into three main groups: cellular, antibody and cytokine.Cellular therapies involve the removal of immune cells from the blood or from a tumor. Immune cells specific for the tumor are activated, cultured and returned to the patient where the immune cells attack the cancer. Cytotoxic T cells and dendritic cells can be used in cell-based immunotherapy. This study is for patients that have a stage Ⅳ gastric cancer with elevated serum CEA concentration. This research study uses special immune system cells called CEA-specific cytotoxic T lymphocytes , a new experimental therapy. Blood will be collected from the patient and the CEA-specific CTLs will be made.The cells will be injected by IV into the patient.The investigators will follow the patient from their last infusion,monitor side effects of immunotherapy and learn more about the way the T cells are working in the patient's body.The investigators will use blood samples to see how long the T cells last and to look at the immune response to the patient's response to cancer.

Official Title
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Phase 1 Study of CEA Specific Cytotoxic T Lymphocytes Induced by Dendritic Cells Infected by Recombinant Adeno-associated Virus With CEA Gene in Stage IV Gastric Cancer

Conditions
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Gastric Cancer

Intervention / Treatment
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* Biological: CTL


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Any patient, at least 18 yrs old regardless of sex, with a diagnosis of Stage IV Gastric Cancer Patients with life expectancy greater than or equal to 6 weeks. Patients with a Karnofsky score of greater than or equal to 80. serum CEA ≥ 20ng/ml. Patient provides consent for all required biopsies. Exclusion Criteria: Patients with severe active infection. Patients receiving systemic corticosteroid within 48 hours of CTL infusion. Patients with HBV,HCV,HIV infection.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CEA Specific CTL<br>Patients receiving CEA-specific CTLs as therapy for Gastric Cancer | Biological: CTL<br>* Mononuclear cells (Dendritic Cell,DC precursor) were isolated from the peripheral blood of gasric cancer by density gradient centrifugation and infected with rAAV/CEA virus.Maturation of the DC was induced by granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-4 (IL-4) and tumor necrosis factor-alpha(TNF-alpha). On day 7, the DCs were collected and mixed with T cells at the ratio of 1 to 20 to induce cytotoxic T lymphocytes (CTL).The cells will be proliferated and infused by intravenous (IV) infusion into the patient.<br>* Other names: CEA Specific Cytotoxic T-Lymphocytes;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ELISPOT assays | Enzyme-Linked ImmunoSpot (ELISPOT) assay is used for monitoring CEA specific cellular immune responses in Gastric Cancer | 1 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| overall survival (OS) |  | 1 month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Dendritic Cells, Cytotoxic T-Lymphocytes, Adeno-Associated Virus