A Phase I Clinical Trial of CAR-T Cells for Advanced Gynecological Solid Tumors

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.