Dual-Target CAR-NK Cells for Advanced Breast Cancer (HER2+ and TNBC)

Inclusion Criteria

• •Histologically confirmed breast carcinoma that is locally advanced, unresectable, or metastatic.
• •Disease subtype: HER2-positive breast cancer or triple-negative breast cancer (TNBC).
• •Progression after, intolerance to, or ineligibility for standard therapies appropriate for the disease subtype and line of therapy.
• •At least one measurable lesion per RECIST v1.1.
• •Tumor antigen assessment available (fresh or archival): expression of at least one candidate target antigen (HER2/ERBB2, MUC1, or ROR1). For TNBC, mesothelin assessment may be performed for exploratory analyses.
• •ECOG performance status 0-1.
• •Adequate organ function (example thresholds): ANC ≥ 1.0 x 10\^9/L; platelets ≥ 75 x 10\^9/L; hemoglobin
• •* 8 g/dL; AST/ALT ≤ 3x ULN (≤ 5x with liver metastases); total bilirubin ≤ 1.5x ULN; creatinine clearance
• •* 50 mL/min.
• •Left ventricular ejection fraction (LVEF) ≥ 45% and no uncontrolled cardiac arrhythmia.
• •Negative pregnancy test for participants of childbearing potential; agreement to use effective contraception during study treatment and for 6 months after last CAR-NK infusion.
• •Ability to understand and willingness to sign informed consent.
• •Prior gene-modified cellular therapy (e.g., CAR-T or CAR-NK) within 6 months or unresolved grade ≥ 2 toxicity from prior cellular therapy.
• •Clinically significant active autoimmune disease requiring systemic immunosuppression (physiologic steroid replacement permitted).
• •Uncontrolled infection, including uncontrolled HBV, HCV, or HIV infection (controlled infections may be eligible per investigator).
• •History of severe hypersensitivity to fludarabine or cyclophosphamide.
• •Pregnant or breastfeeding.
• •Concurrent participation in another interventional study that could confound safety or efficacy assessments.
• •Any condition that, in the investigator's judgment, would make the participant unsuitable for the study (e.g., uncontrolled comorbidity, inability to comply with protocol procedures).