Hepatotoxicity in cancer patients receiving erb-38, a recombinant immunotoxin that targets the erbB2 receptor

To exploit overexpression of erbB2 in human cancers, we constructed a singl e-chain immunotoxin (erb-38) that contains the Fv portion of monoclonal ant ibody e23 fused to a truncated form of Pseudomonas exotoxin A. In a Phase I study, five breast cancer patients and one esophageal cancer patient recei ved three doses of erb-38 at 1.0 and 2.0 mu g/kg, Hepatotoxicity was observ ed in all patients. Immunohistochemistry showed the presence of erbB2 on he patocytes explaining the liver toxicity of erb-38, We suggest that targetin g of tumors with antibodies to erbB2 armed with radioisotopes or other toxi c agents may result in unexpected organ toxicities due to erbB2 on normal c ells.