neoantigen reactive t cells c for chinese patients with advanced gastric cancer

Conditions: Advanced Gastric Cancer

Summary: 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.

Eligibility criteria:
inclusion criteria: 1. voluntarily join the study and sign the informed consent; 2. age: 18-75 years old, male or female; 3. subjects with advanced gastric cancer who had received systematic standard treatment before enrollment and had no effective treatment at present. (note: the effective treatment means refer to the latest version of the "gastric cancer diagnosis and treatment guide" issued by china's "chinese clinical oncology society".) ; 4. have at least one measurable lesion according to imrecist evaluation criteria; 5. expected survival ≥5 months (starting from the collection of tissue samples for sequencing); 6. the eastern cancer consortium (ecog) score was 0 or 1 or 2; 7. the following hematological indicators should be met: neutrophil count ≥ 1.5×109/l; hemoglobin ≥ 10.0 g/dl; platelet count ≥ 50×109/l; 8. the following biochemical indicators should be met: total bilirubin ≤2.0× upper limit of normal value (uln); ast and alt ≤2.0×uln; serum creatinine ≤1.5×uln. 9. before lymphocyte clearance preadministration: 1) any chemotherapy, small molecule targeted drugs and other antitumor therapy received have passed the 3-week washout period, and the toxic side effects have returned to grade 1 or lower (excluding hair loss, vitiligo and other events as determined by the investigator to be tolerated); 2) if surgical treatment is performed within 3 weeks, toxicity has returned to grade 1 or lower; 3) the immunotoxicity of major organs has returned to grade 1 or lower after receiving any antibody drug treatment, and the washout period of pd-1 antibodies has reached 6 weeks, and ctla-4 antibodies and other antibodies have passed the washout period of 4 weeks. exclusion criteria: 1. subjects infected with hbv, hcv, hiv, syphilis and tuberculosis; 2. uncontrolled coronary artery disease or asthma, uncontrolled cerebrovascular disease or what the investigator considers other diseases not included in the group; 3. patients with a history of bone marrow or organ transplantation; patients with coagulation dysfunction; 4. patients with immune deficiency diseases or autoimmune diseases who are treated with immunosuppressive drugs; 5. central nervous system (cns) metastatic and/or cancerous meningitis; 6. people who may be allergic to immunotherapy; 7. drug abuse, clinical or psychological or social factors that affect informed consent or the conduct of the study; 8. pregnant and lactating women; 9. participating in other clinical trials; 10. an uncertainty that the investigator believes has an impact on the subject's safety or compliance.