Phase I Trial of CEA Specific AAV-DC-CTL Treatment in Stage IV Gastric Cancer
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
Study Overview
Detailed Description
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.
Study Type
Enrollment (Anticipated)
Phase
- Phase 1
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NA
- Interventional Model: SINGLE_GROUP
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
EXPERIMENTAL: CEA Specific CTL
Patients receiving CEA-specific CTLs as therapy for Gastric Cancer
|
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.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
ELISPOT assays
Time Frame: 1 month
|
Enzyme-Linked ImmunoSpot (ELISPOT) assay is used for monitoring CEA specific cellular immune responses in Gastric Cancer
|
1 month
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
|---|---|
|
overall survival (OS)
Time Frame: 1 month
|
1 month
|
Collaborators and Investigators
Investigators
- Study Chair: Wu Changping, M.D, The First People's Hospital of Changzhou
Publications and helpful links
General Publications
- Caruana I, Weber G, Ballard BC, Wood MS, Savoldo B, Dotti G. K562-Derived Whole-Cell Vaccine Enhances Antitumor Responses of CAR-Redirected Virus-Specific Cytotoxic T Lymphocytes In Vivo. Clin Cancer Res. 2015 Jul 1;21(13):2952-62. doi: 10.1158/1078-0432.CCR-14-2998. Epub 2015 Feb 17.
- Cui H, Zhang W, Hu W, Liu K, Wang T, Ma N, Liu X, Liu Y, Jiang Y. Recombinant mammaglobin A adenovirus-infected dendritic cells induce mammaglobin A-specific CD8+ cytotoxic T lymphocytes against breast cancer cells in vitro. PLoS One. 2013 May 1;8(5):e63055. doi: 10.1371/journal.pone.0063055. Print 2013.
- Martino AT, Basner-Tschakarjan E, Markusic DM, Finn JD, Hinderer C, Zhou S, Ostrov DA, Srivastava A, Ertl HC, Terhorst C, High KA, Mingozzi F, Herzog RW. Engineered AAV vector minimizes in vivo targeting of transduced hepatocytes by capsid-specific CD8+ T cells. Blood. 2013 Mar 21;121(12):2224-33. doi: 10.1182/blood-2012-10-460733. Epub 2013 Jan 16.
Study record dates
Study Major Dates
Study Start
Primary Completion (ANTICIPATED)
Study Completion (ANTICIPATED)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ESTIMATE)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- CZYY-CTL-001
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