Dual-targeting CAR-T therapy for advanced cancer patients with pleural or peritoneal metastases

* Inclusion Criteria

  1. Male or female participants aged 18 to 75 years. Participants older than 75 years may be enrolled at the investigator's discretion based on overall health status.
  2. Females of childbearing potential must have a negative serum or urine pregnancy test. Females who have undergone surgical sterilization or have been postmenopausal for at least 2 years are considered not of childbearing potential.
  3. Histologically or cytologically confirmed advanced solid tumors with evidence of serosal cavity metastasis (pleural/peritoneal) and/or leptomeningeal metastasis, who have failed standard-of-care therapies.For leptomeningeal metastasis: patients must have received at least 3 intrathecal chemotherapy infusions with persistent positive CSF cytology and neurological symptoms, OR have re-positivity of CSF cytology after prior clearance.
  4. Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
  5. Life expectancy \> 3 months.
  6. Adequate organ and bone marrow function:

     Absolute neutrophil count ≥ 1.5 × 10⁹/L Platelets ≥ 90 × 10⁹/L Absolute lymphocyte count ≥ 1.0 × 10⁸/L Hemoglobin ≥ 9.0 g/dL ALT/AST ≤ 2.5 × ULN (≤ 5 × ULN for patients with liver metastases) Total bilirubin ≤ 1.5 × ULN Creatinine \< 1.5 × ULN AND creatinine clearance ≥ 50 mL/min (Cockcroft-Gault formula). Creatinine clearance assessment is required only when creatinine ≥ 1.5 × ULN.
  7. Cardiac ejection fraction ≥ 50%. Patients with minimal or moderate pericardial effusion may be enrolled at the investigator's discretion.
  8. No other severe concurrent diseases (e.g., active autoimmune diseases, immunodeficiency).
  9. Chemotherapy must be discontinued for at least 3 weeks prior to CAR-T cell infusion.
  10. Sexually active participants of childbearing potential must agree to use highly effective contraceptive methods from screening through 1 year after CAR-T cell infusion.
  11. Voluntary participation with written informed consent obtained prior to any study-specific procedures.
  12. Recovery from prior antitumor therapy to ≤ Grade 1 (CTCAE v5.0), except for alopecia, hormone-replacement-controlled hypothyroidism, Grade 2 peripheral neuropathy, vitiligo, well-controlled diabetes, or other chronic toxicities deemed by the investigator to be stable and not interfering with study conduct.
* Exclusion Criteria

  1. Known hypersensitivity to cytokines.
  2. Active infection requiring systemic anti-infective therapy.
  3. Acute or chronic graft-versus-host disease (GVHD).
  4. History of malignancies other than the target indication within 5 years prior to screening, with the exception of adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the breast after curative resection.
  5. Active hepatitis B or C, or HIV infection. HBsAg-positive patients may be enrolled if HBV DNA is below the lower limit of normal (LLN) per institutional standard; HCV antibody-positive patients may be enrolled if HCV RNA is below LLN per institutional standard. Carriers require antiviral therapy as clinically indicated and periodic quantitative nucleic acid testing during the study.
  6. Prior immunotherapy-related adverse event of Grade ≥ 3, or any other concurrent disease, metabolic dysfunction, physical examination finding, or laboratory abnormality that would reasonably preclude use of the investigational product, confound study results, or place the participant at undue risk.
  7. Clinically significant cardiovascular disease, including but not limited to:Congestive heart failure (NYHA Class \> 2);Unstable angina;Myocardial infarction within the past 3 months;Supraventricular or ventricular arrhythmia requiring treatment or intervention;Poorly controlled Grade 2-3 hypertension
  8. Known psychiatric disorders, alcoholism, drug abuse, or substance dependence that may interfere with study compliance.
  9. Active autoimmune disease, history of autoimmune disease, or condition requiring systemic corticosteroids (\> 10 mg/day prednisone or equivalent) or immunosuppressive therapy (e.g., post-organ transplantation). Inhaled corticosteroids are permitted.
  10. Unstable pulmonary embolism, deep vein thrombosis, or other major arterial/venous thromboembolic events within 6 months prior to enrollment. Patients on anticoagulation therapy must be on a stable dose prior to enrollment.
  11. Pregnant or lactating women, or women planning pregnancy during the treatment period or within 1 year after CAR-T cell infusion.Women of childbearing potential unwilling to use highly effective contraception during the treatment period and for 1 year after CAR-T cell infusion. A negative serum or urine pregnancy test (within 48 hours prior to treatment) is required for women of childbearing potential.
  12. Any condition that, in the investigator's opinion, precludes the participant from providing written informed consent or complying with study procedures.
  13. Any other condition deemed by the investigator as inappropriate for study participation.