One of the most important CAR-T treatment-related side effects is “on-target, off-tumor toxicity”, Substantial evidence of “on-target, off-tumor toxicity” has been shown in CAIX-directed CAR-T (6), FAP-directed CAR-T (7), CD19-directed CAR-T (2), CD133-directed CAR-T (26), HER2-directed CAR-T (27), EGFR-directed CAR-T (28), CD38-directed CAR-T (3), CD138-directed CAR-T (29), CD33-directed CAR-T (30–32), and CD123-directed CAR-T (33, 34). The gene discussed is PROM1; the disease is neoplasm.