Células CAR-T dirigidas a MUC1 para tumores ginecológicos avanzados

Fecha de inicio: 11 de mayo de 2025

inclusion criteria 1. Patients with gynecological solid tumors diagnosed by histopathology, with tumor tissue sample MUC1 expression rate ≥50% or MSLN expression rate ≥50%, PD-L1 positive expression, and sample source within 2 years; 2. Patients with advanced gynecological solid tumors who have failed standard treatment or are intolerant to such treatment and have no standard effective treatment options; 3. Females aged 18 to 70 years (inclusive); 4. Estimated survival time ≥ 3 months; 5. ECOG performance status score of 0 to 1 at screening and baseline; 6. Good organ and bone marrow function: 1. The researcher assesses sufficient bone marrow function to receive lymphocyte-depleting chemotherapy: Neutrophil count ≥1.5 × 10\^9/L, lymphocyte count ≥0.5 × 10\^9/L; 2. Platelet count ≥90 × 10\^9/L; 3. Hemoglobin ≥90 g/L (no blood transfusion or no erythropoietin-dependent within 7 days); 4. Total bilirubin ≤2 times the upper limit of normal value; 5. Serum creatinine ≤1.5 times the upper limit of normal value; 6. Transaminase (AST, ALT) ≤2.5 times the upper limit of normal value (if liver metastasis is present, 5 times the upper limit of normal value); 7. International Normalized Ratio (INR) or prothrombin time (PT) ≤1.5 times the upper limit of normal value; 8. Pulmonary function: ≤ CTCAE grade 1 dyspnea and SaO2 ≥ 91% in room air; 9. Cardiac function: Echocardiogram or radionuclide ventriculography (MUGA) assessment left ventricular ejection fraction (LVEF) ≥50% within 1 month of enrollment. exclusion criteria 1. Participants who have undergone other anti-tumor treatments not allowed by the protocol within 1 month before CAR-T infusion (including radiotherapy, chemotherapy, small molecules, biological treatment, or immunotherapy, other research drugs); 2. Participants who have previously received targeted therapy against MUC1 or MSLN, or cellular therapy, or any gene therapy products (including CAR-T cell therapy) or any T cell therapy at home or abroad; 3. Pregnant or breastfeeding women; 4. AIDS virus, syphilis seroreactivity positive; hepatitis B surface antigen positive, or hepatitis B core antibody positive and hepatitis B virus DNA copies higher than the detection limit or greater than or equal to 1000 copies/mL; or hepatitis C virus infection; 5. Any uncontrollable active infection, coagulopathy, or any other major disease; 6. Patients with active autoimmune diseases being treated, organ transplantation and other immune-related diseases, or long-term use of immunosuppressive drugs such as glucocorticoids: a. Glucocorticoids cannot be discontinued within 72 hours before CAR-T cell infusion; b. Immunosuppressive agents other than glucocorticoids cannot be discontinued ≥4 weeks before enrollment; 7. Patients with severe cardiopulmonary insufficiency, uncontrolled hypertension, any of the following cardiovascular disease histories within the past 6 months: III or IV heart failure defined by the New York Heart Association (NYHA), cardiac catheterization or stent, myocardial infarction, unstable angina, or other clinically significant heart disease; 8. Patients with confirmed brain metastasis, or those with a history of or current central nervous system disease, such as epileptic seizures, cerebrovascular ischemia/hemorrhage, dementia, encephalopathy, or any autoimmune disease associated with the central nervous system; 9. Patients with high risk of bleeding or perforation; 10. Patients who underwent major surgery or significant trauma within 4 weeks before single collection; 11. Patients with other malignant tumors within 3 years or concurrently (except for skin basal cell carcinoma, cervical/breast cancer in situ, etc.); 12. Any other conditions deemed unsuitable for participation in the study by the investigator.