Comparative preclinical activity of the folate-targeted Vinca alkaloid conjugates EC140 and EC145
Article first published online: 5 JUN 2007
Copyright © 2007 Wiley-Liss, Inc.
International Journal of Cancer
Volume 121, Issue 7, pages 1585–1592, 1 October 2007
How to Cite
Leamon, C. P., Reddy, J. A., Vlahov, I. R., Westrick, E., Parker, N., Nicoson, J. S. and Vetzel, M. (2007), Comparative preclinical activity of the folate-targeted Vinca alkaloid conjugates EC140 and EC145. Int. J. Cancer, 121: 1585–1592. doi: 10.1002/ijc.22853
- Issue published online: 24 JUL 2007
- Article first published online: 5 JUN 2007
- Manuscript Accepted: 23 MAR 2007
- Manuscript Received: 18 JAN 2007
- Indiana 21st Century Fund. Grant Number: 511040805
- folate receptor;
- Vinca alkaloid
EC140 is a water soluble folate conjugate of desacetylvinblastine monohydrazide (DAVLBH), which is constructed with an endosome-cleavable acyl hydrazone bond. This agent has proven to be active and specific against well established, subcutaneous folate receptor (FR)-positive tumors in multiple animal models. Recent structure-activity and optimization studies have yielded a disulfide bond-containing counterpart to EC140, herein referred to as EC145. This new conjugate was found to retain high affinity for FR-positive cells, and it produced specific, dose-responsive activity in vitro. Comparative in vivo efficacy tests confirmed that, like EC140, EC145 displays activity against both syngeneic and xenograft tumor models. However, EC145 was found to be more active and better tolerated than EC140; hence, more durable complete responses were consistently observed in EC145-treated tumor-bearing animals. Furthermore, EC145 was not found to be active against a FR-negative tumor model. Additional preclinical studies are therefore warranted to better understand EC145's breadth of activity against FR-positive tumors. © 2007 Wiley-Liss, Inc.