Dual-Target MSLN/FAP CAR-NK Cells for Pleural and Peritoneal Mesothelioma

Inclusion Criteria:

* Age 18 to 75 years at the time of consent.
* Histologically confirmed malignant pleural mesothelioma or malignant peritoneal mesothelioma; unresectable, recurrent, metastatic, or refractory disease.
* Prior receipt of at least one standard systemic regimen for mesothelioma, or documented ineligibility, intolerance, or refusal of standard therapy considered reasonable by the investigator.
* Central biomarker confirmation of MSLN-positive tumor cells and FAP-positive tumorassociated stroma at protocol-defined thresholds.
* At least one measurable or evaluable lesion by cohort-appropriate imaging criteria.
* ECOG performance status 0 to 1.
* Adequate bone marrow, renal, hepatic, coagulation, cardiac, and pulmonary function to undergo lymphodepletion and locoregional cell infusion.
* Safe procedural access for intrapleural or intraperitoneal administration, as applicable.
* Recovery to Grade 1 or better from prior anticancer therapy toxicities, except alopecia, stable neuropathy, or controlled endocrine replacement.
* Life expectancy of at least 12 weeks.
* Negative pregnancy test for participants of childbearing potential and agreement to use protocoldefined contraception.
* Ability to understand and sign informed consent

Exclusion Criteria:

* Active or untreated CNS metastases, leptomeningeal disease, or uncontrolled seizures.
* Uncontrolled bacterial, fungal, viral, or mycobacterial infection, including empyema, active pleural space infection, peritonitis, or uncontrolled HBV, HCV, or HIV infection.
* Autoimmune disease requiring systemic immunosuppression within 14 days before lymphodepletion, or prednisone equivalent greater than 10 mg/day.
* Clinically significant cardiovascular disease, uncontrolled arrhythmia, unstable angina, recent myocardial infarction, or other condition judged to increase infusion risk.
* Severe interstitial lung disease, baseline oxygen requirement, or other pulmonary compromise making pleural therapy unsafe.
* Bowel perforation risk, uncontrolled bowel obstruction, uncontrolled ascites, or any abdominal condition that makes intraperitoneal infusion unsafe in the peritoneal cohort.
* Prior gene-modified cell therapy directed against MSLN or FAP within the protocol washout period, or active graft-versus-host disease after prior transplant.
* Need for concurrent systemic anticancer therapy other than protocol-permitted supportive care.
* Pregnancy or breastfeeding.
* Any medical, psychiatric, social, or logistical condition that, in the investigator's judgment, could compromise safety, compliance, or interpretability of study results.