Biomarker-Guided Dual-Target CAR-T Cells for Advanced Solid Tumors

Inclusion Criteria:

* Age 18-75 years at consent
* Histologically or cytologically confirmed advanced unresectable, metastatic, or recurrent solid malignancy (including recurrent high-grade glioma for CNSspecific pairs) for which standard curative therapy does not exist, is not tolerated, or has failed.
* At least one predefined dual-target pair qualifies on central biomarker review. Recommended working thresholds: primary antigen \>= 2+ intensity in \>= 50% of viable tumor cells (or pair-specific equivalent) AND secondary antigen detectable in \>= 25% of viable tumor cells, with acceptable normal-tissue risk after pathology review
* At least 1 measurable lesion by RECIST 1.1, or measurable / evaluable disease by RANO for CNS cohorts.
* ECOG performance status 0-1 (CNS cohort may allow Karnofsky \>= 70 or ECOG 0-2 if justified).
* Adequate organ function: ANC \>= 1.0 x 10\^9/L, platelets \>= 75 x 10\^9/L, hemoglobin \>= 8 g/dL, creatinine clearance \>= 50 mL/min, AST / ALT \<= 3 x ULN (\<= 5 x ULN if liver involvement), total bilirubin \<= 1.5 x ULN unless Gilbert syndrome, LVEF \>= 45%, oxygen saturation \>= 92% on room air.
* Recovered to Grade \<= 1 from acute toxicities of prior anticancer therapy (except alopecia, stable endocrinopathies, or other protocol-allowed residual toxicities).
* Adequate venous access and ability to undergo leukapheresis; successful manufacture of a release-qualified autologous dual-target CAR-T product.
* Life expectancy \>= 12 weeks.
* Negative pregnancy test for persons of childbearing potential and agreement to use highly effective contraception per protocol.
* Ability to understand and sign informed consent and comply with study follow-up, including long-term gene-modified cell monitoring.

Exclusion Criteria:

* No qualifying target pair after central review, or target pair considered unsafe because of unacceptable predicted ontarget / off-tumor risk.
* Prior gene-modified cellular therapy directed against the same target pair within 6 months, or persistent clinically significant toxicity from prior cell / gene therapy.
* Active uncontrolled infection, including uncontrolled bacterial, fungal, or viral infection; active tuberculosis; uncontrolled HIV; active hepatitis B or C with detectable / unsafe viral burden.
* Need for systemic corticosteroids \> 10 mg prednisone equivalent daily or other systemic immunosuppressive therapy within 7 days before lymphodepletion, unless specifically allowed for physiologic replacement or CNS edema management per cohort rules.
* Active autoimmune disease requiring systemic immunosuppression within the past 2 years, except protocol-allowed stable conditions.
* Clinically significant cardiovascular disease (for example uncontrolled arrhythmia, recent myocardial infarction, unstable angina, decompensated heart failure), severe pulmonary compromise, or other major comorbidity making cell therapy unsafe.
* Active symptomatic CNS hemorrhage, uncontrolled seizures, or uncontrolled intracranial hypertension; leptomeningeal disease requiring urgent intervention unless explicitly allowed in a CNS-specific cohort.
* Pregnancy or breastfeeding.
* Concurrent second malignancy requiring active systemic treatment, except certain low-risk or definitively treated cancers allowed by protocol.
* Any condition that, in the investigator's judgment, would interfere with safe participation, product manufacture, infusion, or interpretation of results.