Biomarker-Guided Allogeneic Single-Target or Dual-Target CAR-NK Cell Therapy for Advanced Solid Tumors

This is an open-label, biomarker-driven adoptive cell therapy study. Screening / Target Selection (Precision Step): Participants undergo tumor antigen profiling using: Tissue biopsy (preferred when safely feasible), and/or Liquid biopsy (e.g., circulating tumor DNA plus circulating tumor cells/exosome protein assay, as available in the platform). Antigen profiling determines eligibility and assigns participants to: Single-target CAR-NK if one antigen meets positivity thresholds, or Dual-target CAR-NK if two antigens meet thresholds or if heterogeneity is suspected. Pre-specified target menu : TROP2, Mesothelin (MSLN), B7-H3 (CD276), HER2, EGFR, GD2, Claudin18.2, GPC3, PSMA ("Target menu" can be expanded in amendments.) Cell Source / Manufacturing Concept: NK cells are obtained from a healthy allogeneic donor (unrelated or partially matched per site policy). Donor NK cells are collected by leukapheresis, activated/expanded, and genetically modified to express: a single CAR (Arm A) or a dual CAR / dual-target construct (Arm B). Final product is cryopreserved and released after sterility/identity/potency testing. Conditioning \& Treatment: Participants receive lymphodepleting chemotherapy followed by CAR-NK infusion(s). Many CAR-NK solid-tumor trials use conditioning regimens such as fludarabine and cyclophosphamide before infusion. Optional cytokine support (e.g., low-dose IL-2) may be used per protocol to support NK persistence, consistent with approaches used in some CAR-NK studies. Follow-up: Intensive safety monitoring during the first 28 days. Tumor imaging at protocol-defined intervals. Correlative studies including CAR-NK persistence and ctDNA dynamics.