Initial testing (Stage 1) of the antibody-maytansinoid conjugate, IMGN901 (Lorvotuzumab mertansine), by the pediatric preclinical testing program.

摘要: Background IMGN901 (lorvotuzumab mertansine) is an antibody-drug conjugate composed of a humanized antibody that specifically binds to CD56 (NCAM, neural cell adhesion molecule) and conjugated the maytansinoid, DM1 (a microtubule targeting agent). Procedures IMGN901 DM1-SMe (unconjugated as mixed disulfide with thiomethane cap its sulfhydryl group) were tested in vitro at concentrations ranging from 0.01 nM 0.1 µM 0.3 pM 3 nM, respectively. IMGN901 was against subset PPTP solid tumor xenografts focusing on those high expression.The combination topotecan also evaluated. Results Neuroblastoma models expressed or above median expression level for all lines. Neuroblastoma lines demonstrated relatively low sensitivity compared other lines, but neuroblastoma comparable non-neuroblastoma In vivo, objective responses observed 9 24 (38%) including, three seven xenografts, two rhabdomyosarcoma xenografts. All showed homogeneous high-level staining by IHC CD56, not homogenous had responses. Combined topotecan, therapeutic enhancement four models. Conclusions IMGN901 has anti-tumor activity some expressing pediatric cancer models. High biomarker vivo response, resistance mechanisms need be defined. Pediatr Blood Cancer 2013;60:1860–1867. © 2013 Wiley Periodicals, Inc.