This is a multicenter, open-label, Phase 1/2 master protocol evaluating autologous dual-target CAR-T cell therapy in adults with advanced solid cancers. After central biomarker screening, each participant is assigned the best-matched dual-target construct from a predefined target-pair library. The trial is designed to test whether biomarkerguided dual targeting can improve tumor control, reduce antigenescape risk, and preserve safety in solid tumors.

Participants undergo central pathology review and antigen profiling on fresh or archived tumor tissue. If one or more predefined dual-target pairs qualify, a target-selection committee ranks candidate pairs using

(1) co-expression level, (2) tumor-normal differential, (3) diseasespecific biologic rationale, and (4) product / manufacturing feasibility.

All enrolled participants receive lymphodepletion with fludarabine and cyclophosphamide followed by one infusion of the assigned autologous dual-target CAR-T product. Each newly activated target-pair cohort begins with dose escalation (modified 3+3 lead-in) and, if acceptable, proceeds to dose expansion at the recommended Phase 2 dose / schedule (RP2D / RP2S). Optional repeat infusion is allowed for selected participants with retained eligibility, available product, and no prohibitive toxicity. Disease response is assessed by RECIST 1.1 for non-CNS disease and by RANO for CNS cohorts. Participants are followed for disease outcomes for 24 months and for long-term genemodified cell safety for up to 15 years, consistent with local genetherapy follow-up expectations. Because the solid-tumor target landscape continues to evolve, this example uses a broad predefined target library rather than claiming to be a permanently exhaustive list of every future target.

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.

Not masked because construct selection, manufacturing release, doseescalation decisions, and acute cell-therapy toxicity monitoring require investigator awareness.