Sequential Infusion of CD146-Targeted and HER2-Targeted CAR T Cells in Patients With Advanced Sarcomas

Inclusion Criteria: * Expected survival time ≥3 months; * Diagnosis: Histologically or cytologically confirmed sarcoma (soft tissue or bone sarcoma), that is metastatic, locally advanced, or refractory to standard therapy. This may include osteosarcoma, Ewing sarcoma, rhabdomyosarcoma, leiomyosarcoma, or other high-grade sarcomas. Patients must have evidence of measurable disease as per RECIST or applicable criteria. * Prior Treatment: Patients should have received and progressed on or not be candidates for standard first-line treatments. There is no limit on number of prior lines of therapy, but at least one prior systemic therapy for sarcoma is typically required (unless no standard therapy exists for the subtype). A minimum wash-out period (e.g. 2 weeks) from previous treatments (chemotherapy, radiation, or other immunotherapy) is required before lymphodepletion. * Age and Performance Status: Participants age 12 years and older (both adolescent and adult patients are eligible; for minors, legal guardian consent is required). Upper age limit of \~75 years, or as determined by medical fitness. ECOG performance status 0-1 (or Karnofsky ≥70% for pediatric patients), indicating subjects are ambulatory and able to perform light work. * Organ Function: Adequate organ function to undergo cytotoxic chemotherapy and cell transfer therapy, including: cardiac ejection fraction ≥50%; baseline oxygen saturation \>92% on room air; adequate bone marrow reserves (absolute neutrophil count ≥1.0×10\^9/L, platelets ≥75×10\^9/L, hemoglobin ≥8 g/dL), hepatic function (e.g. bilirubin ≤1.5× ULN, AST/ALT ≤2.5× ULN), and renal function (e.g. creatinine clearance ≥50 mL/min or age-appropriate normal). * Tumor Antigen Expression: Expression of CD146 and/or HER2 in the tumor is recommended (as assessed by immunohistochemistry or flow cytometry on a tumor sample). Note: At least one of the target antigens (CD146 or HER2) should be present on the tumor; if feasible, patients should have tumor tissue tested for these markers. (In cases where testing is unavailable, enrollment may proceed based on histology known to often express these targets, per investigator judgment.) * Consent: Ability to understand and provide written informed consent (or assent for minors with consent of legal guardian). Patients (or guardians) must be willing to comply with trial procedures and follow-up. Exclusion Criteria: * Recent Therapies: Prior treatment with any CAR-T cell therapy or other gene-modified T-cell therapy is excluded. Also exclude patients who received any investigational drug, immunotherapy (e.g. checkpoint inhibitor), or major surgery within a certain interval (e.g. 4 weeks) prior to enrollment. Concurrent enrollment in another interventional clinical trial is not allowed. * Recent Therapies: Prior treatment with any CAR-T cell therapy or other gene-modified T-cell Infections: Active uncontrolled infection, including active hepatitis B or C infection, or HIV infection with uncontrolled viral load. Patients must not have evidence of active tuberculosis or other severe infections. All patients will be screened for HBV, HCV, and HIV at baseline. * Immunosuppression: Use of systemic immunosuppressive medications (such as chronic corticosteroids at \>10 mg prednisone daily or equivalent) within 7 days prior to leukapheresis. (Physiologic replacement doses of steroids are permitted.) Patients with a history of allogeneic stem cell transplant or solid organ transplant are excluded (due to the need for immunosuppression and risk of graft-versus-host or graft rejection). * Medical Comorbidities: Any significant uncontrolled medical condition that would, in the investigator's judgment, make the patient an unsuitable candidate for CAR-T therapy. For example: active autoimmune diseases requiring immunosuppression, clinically significant heart failure (NYHA class III-IV), unstable angina or myocardial infarction within 6 months, severe chronic respiratory disease requiring supplemental oxygen, or psychiatric conditions that would interfere with study participation and follow-up. * Pregnancy/Breastfeeding: Women who are pregnant or breastfeeding are excluded due to unknown risks of the treatment to a fetus or infant. Female participants of childbearing potential and male participants with partners of childbearing potential must agree to use effective contraception during the study and for a suitable period after CAR-T infusion (e.g. 1 year), given the potential for sustained CAR T-cell activity. A negative serum pregnancy test is required for females of childbearing potential before starting lymphodepletion.