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The purpose of this study is to see the safety and efficient of neoantigen reactive T cells (NRTs) in the treatment of Chinese patients with advanced gastric cancer.
The tumor-specific "none-self" immunogenic neoantigens encoded by either viral genes or somatic mutation genes, possess the potential to induce specific anti-cancer immunity, including cellular and humoral immune responses. Today, numerous clinical trials demonstrate that although these "none-self" antigens initiate the antigen-specific immunoglobulin G antibodies and cluster of differentiation 4(CD4)+/cluster of differentiation 8(CD8)+T-cells response, not all of them show a clinical benefit in the response rate, progression-free survival or overall survival.Personalized cell therapy maybe own a breakthrough in the treatment of those gastric cancer patients without standard options.The investigators' center has successfully established a new method for preparing personalized neoantigen reactive T cells(NRTS) for adoptive cell therapy(ACT). Today, the investigators will carry out a single arm clinical prospective study of NRTs for the treatment of Chinese patients with advanced gastric cancer. Participants are assigned to receive 4 circles of cell therapy, and IL-2 continuous intravenous infusion(CIV) will also be given for 5 consecutive days after each time's cell infusion. The safety and clinical response rate(RR) are evaluated. Biomarkers and immunological markers are also monitored.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Neoantigen Reactive T Cells | Experimental | Peripheral blood lymphocytes will be collected and neoantigen reactive T cells(NRTs) will be generated in the laboratory;nab-paclitaxel 100-200mg/m2/D will be i.v. for 7 days before cell infusion; Cyclophosphamide 300mg/m2/D will be i.v. for 2 and 3 days before cell infusion; NRTs 0.5~1 x 10^10, will be i.v.Q3 weeks for total 4 doses;Interleukin-2 (IL-2) will be continuous intravenous infused since the first day of the cell infusion for 5 consecutive days, 1000,000 international unit per day.All Patients will receive a total of 4 cycles of treatment. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Neoantigen Reactive T Cells(NRTs) | Biological | Neoantigen Reactive T Cells in an expected volume of 100 milliliter(mL) will be given by intravenous injection over 2-10 minutes through either a peripheral or a central line. |
| Measure | Description | Time Frame |
|---|---|---|
| Number of participants with Adverse Events | using Common Terminology Criteria for Adverse Events (CTCAE v4.0) in patients | up to 6 months |
| Measure | Description | Time Frame |
|---|---|---|
| Response Rate | Response Rate(RR)will be evaluated according Response Evaluation Criteria in Solid Tumors | Visits were conducted at the end (or termination) of each course and at 30, 90, and 120 days after the end of the last course for 4 months |
| Progression free survival (PFS) |
| Measure | Description | Time Frame |
|---|---|---|
| Overall Survival (OS) | the duration is measured from the time of treatment to the time of death | Visits were conducted at the end (or termination) of each course and at 30, 90, and 120 days after the end of the last course for 4 months |
| Interferon-gama change of PBMC cells in the peripheral blood stimulated by tumor antigens |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Xian Shen | Contact | 13968888872 | 13968888872@163.com |
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the duration of progression free survival is measured from the time of treatment to the first date that recurrent or progressive disease or for any reason of death is objectively documented. |
| Visits were conducted at the end (or termination) of each course and at 30, 90, and 120 days after the end of the last course for 4 months |
T cells in the peripheral blood stimulated by tumor antigens for 24 hr,and then Interferon-gama secretion is measured |
| Visits were conducted at the end (or termination) of each course and at 30, 90, and 120 days after the end of the last course for 4 months |