Here, we demonstrate expansion of CPE‐based oncoleaking strategy specifically for tumor types overexpressing claudins, which are not CPE receptors such as Cldn1 by design and use of CPE mutants: In vitro and in vivo, tumor growth of PTC (K1 cells), overexpressing mainly Cldn1, but not Cldn3 and Cldn4, was efficiently reduced by Cldn1‐binding CPE‐variant S231R/S313H (CPE‐Mut3), but not by CPEwt. Here, CLDN3 is linked to neoplasm.