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**p95HER2.CAR-TECH2Hi** is a preclinical, engineered autologous T-cell product developed by the Vall d’Hebron Institute of Oncology in collaboration with Hospital del Mar Research Institute for HER2-amplified solid tumors, particularly HER2-positive breast cancer. The cells express a second-generation CAR directed against p95HER2, a tumor-specific truncated HER2 isoform, and simultaneously produce TECH2Hi, a trastuzumab-derived HER2 × CD3 bispecific T-cell engager. The dual design was intended to combine direct recognition of p95HER2-positive tumor cells with recruitment of additional T cells to HER2-overexpressing tumor cells. However, the high-affinity TECH2Hi engager also recognized physiological HER2 on nonmalignant cells, including cardiomyocytes, producing on-target off-tumor cytotoxicity; development therefore shifted to the lower-affinity p95HER2.CAR-TECH2Me construct.
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