Letter to the editor: efficacy and safety of anti-Trop antibodies, R. Cubas, M. Li, C. Chen and Q. Yao, Biochim Biophys Acta 1796 (2009) 309-1.

Still little information is available on the efficacy and toxicity of anti-Trop-2 antibodies in man. Findings on antibodies anti-Trop-1/Ep-CAM, a paralog molecule of Trop-2, may provide preliminary indications, and a low-affinity anti-Trop-1/Ep-CAM monoclonal antibody, failed to show any benefit in colon cancer patients. Other anti-Trop-1 antibodies, e.g. MT201, may bear more promise, as may more advanced molecular forms, e.g. a BiTE design (MT110) or trifunctional antibodies (catumaxomab). However, the efficacy of these reagents in cancer patients still needs to be proven in randomized clinical trials. As for toxicity, the administration of ING-1, a high-affinity, human-engineered anti-Trop-1/Ep-CAM monoclonal antibody, caused cases of acute pancreatitis. The exocrine pancreas also expresses Trop-2. Hence, similar concerns should apply to the administration of anti-Trop-2 monoclonal antibodies to patients. More in general, contrary to the statements by Cubas et al., Trop-2/T-16/Mov-16 is expressed by several normal tissues in man, e.g. epidermis, exocervix, esophagus, tongue, urothelium, kidney, pancreas, trophoblast and breast. Hence, additional effort is required to develop Trop-2 into a useful immunotherapeutic target, by increasing anti-Trop-2 antibody efficacy, while keeping under control toxicity on expressing normal tissues.