The oncofetal protein, 5T4, is a suitable target for antibody-guided anti-cancer chemotherapy with calicheamicin

• DOI: 10.3892/ijo.32.1.221
• Publication Date: 2014-03-10T03:32:37Z
• Authors: E. Boghaert; L. Sridharan; K. Khandke; D. Armellino; M. Ryan; K. Myers; R. Harrop; A. Kunz; P. Hamann; K. Marquette; M. Dougher; J. DiJoseph; N. Damle
• Keywords: Calicheamicin; Oncofetal antigen; Conjugate; Antibody-drug conjugate

The oncofetal protein, 5T4, is a tumor-associated protein displayed on the cell membrane of various carcinomas. This molecule promising target for anti-tumor vaccine development and targeted therapy with staphylococcus exotoxin. potential use 5T4 as antibody-guided chemotherapy has not been demonstrated. We report oncolytic efficacy selectivity in vitro vivo immuno-conjugates calicheamicin (CM) anti-5T4 antibody, H8. CM potent cytotoxic drug that causes double strand breaks DNA. Conjugates H8 were constructed acid-labile well acid-stabile linkers. In vitro, when applied to monolayers 5T4(+) cells, CM-conjugates targeting consistently more toxic than either free or non-binding control CM-conjugate. difference was less pronounced 5T4-deficient cells. vivo, four 5T4-positive subcutaneous tumor models treated conjugates. Efficacy demonstrated by reduction growth relative controls vehicle. To evidence selectivity, conjugates compared H8, mixture calicheamicin, alone conjugated anti-CD33 hP67.6. addition, an conjugate evaluated orthotopic model lung cancer. Increased survival following treatment used parameter efficacy. Calicheamicin effective selective all examined models. Differences between depended investigated model.