Notably, a clinical trial conducted at NCI to test third-generation HER2 CAR-T cells (CD28/4-1BB/CD3ζ) in patients with metastatic cancers (NCT00924287); however, the trial was terminated after a patient with CRC died of severe acute respiratory failure as a result of the treatment. Here, ERBB2 is linked to metastatic malignant neoplasm.