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

NCT ID: NCT02496273

Last Updated: 2016-02-22

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-01-31
• Study Completion Date: 2030-12-31

Brief Summary

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

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.

Conditions

Gastric Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

CEA Specific CTL

Patients receiving CEA-specific CTLs as therapy for Gastric Cancer

Group Type: EXPERIMENTAL

CTL

Intervention Type: BIOLOGICAL

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.

Interventions

CTL

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.

Intervention Type: BIOLOGICAL

Other Intervention Names

CEA Specific Cytotoxic T-Lymphocytes

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The First People's Hospital of Changzhou

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Wu Changping, M.D

Role: STUDY_CHAIR

The First People's Hospital of Changzhou

References

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.

Reference Type: BACKGROUND

PMID: 25691731 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 23650543 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 23325831 (View on PubMed)

Other Identifiers

CZYY-CTL-001

Identifier Type: -

Identifier Source: org_study_id