tcr-t cells in the treatment of advanced pancreatic cancer

Conditions: Pancreatic Cancer

Summary: to investigate the safety, tolerability, efficacy and pharmacokinetics of tcr-t cells in the treatment of advanced pancreatic cancer

the aim of this clinical trial is to investigate the safety, tolerability, efficacy and pharmacokinetics of tcr-t cell therapy in patients with advanced pancreatic cancer by intravenous injection, in order to explore an effective cellular immunotherapy method for the treatment of advanced pancreatic cancer

Eligibility criteria:
inclusion criteria: * to be eligible for the study, patients must meet all of the following criteria: 1. male or female, aged 18-75 years; 2. patients with advanced pancreatic cancer diagnosed by histology or cytology, patients who failed to respond to standard treatment, relapsed or voluntarily gave up; 3. patients must have tumor tissue that expresses specific tumor antigens, such as mutations in ras and/or tp53; 4. patients must undergo hla matching testing and meet the requirements of hla matching. 5. at least one measurable or evaluable lesion ≥15 mm according to recist1.1 criteria; 6. patients with ecog \< 2 and life expectancy ≥3 months; 7. a) liver function: alt/ast \< 3 times the upper limit of normal value (uln) and bilirubin ≤34.2μmol/l; b) renal function: creatinine \< 220μmol/l; c) terminal oxygen saturation ≥95% in room air; d) cardiac function: left ventricular ejection fraction (lvef) ≥60%; e) blood routine: absolute neutrophil count ≥ 1×109/l; platelet count ≥70×109/l; absolute lymphocyte count ≥100 cells /μl; 8. the patients met the requirements of apheresis without any contraindications. 9. women of childbearing age who have a negative urine pregnancy test at screening and before starting dosing and who have agreed to use highly effective contraception for at least 100 days after infusion; female participants must agree not to donate eggs (oocytes, oocytes) for assisted reproductive purposes during the study and for 90 days after receiving the last study drug; 10. male subjects with a fertile partner must consent to use an effective barrier method of contraception for at least 100 days after infusion; must agree not to donate sperm for at least one year; 11. sign an informed consent form. exclusion criteria: * patients who met any of the following criteria were not eligible for inclusion in the study: 1. persons with severe mental disorders; 2. a positive virological test for any of the following: hiv; hcv; hbsag; hbcab was positive, and hbv dna copy number and tppa were positive. 3. patients with severe allergic history or allergic constitution; 4. severe underlying medical conditions such as evidence of other serious active viral, bacterial or uncontrolled systemic fungal infection; active autoimmune disease or a history of autoimmune disease within 3 years; 5. a history of autoimmune diseases (e.g., crohn's disease, rheumatoid arthritis, systemic lupus erythematosus) leading to end-organ damage or requiring systemic immunosuppressive/systemic disease modulating drugs within the past 2 years; 6. combined with organ dysfunction, such as renal insufficiency; 7. had been enrolled in another clinical trial within 4 weeks before enrollment in the trial; 8. those who were unable to comply with the study protocol and follow-up plan due to physiological, family, social, geographical and other factors; 9. patients with contraindications to cyclophosphamide or fludarabine chemotherapy; 10. subjects who required additional immunosuppressive drug therapy within 72 hours before tcr-t infusion, except for the treatment of adverse events during the trial; 11. pregnant, lactating women, or men who plan to have children while participating in the study or within 100 days of receiving study treatment; 12. any other condition considered by the investigator to be ineligible for enrollment.

Keywords: tcr-t t cells ras tp53 cell therapy