Microencapsulation of an anti-VE-cadherin antibody secreting 1B5 hybridomacells

Accumulating experimental evidence demonstrates that tumor growth and letha lity are dependent on angiogenesis. Based on this concept, there is growing interest in the use of antiangiogenesis agents to inhibit tumor expansion. Compelling data implicate vascular endothelium (VE)-cadherin (an endotheli um specific protein) as a key factor in the last step of angiogenesis, wher e the endothelial cells join one to each other and form microtubules (futur e blood vessels). We propose a novel approach to the inhibition of angiogen esis by immobilizing VE-cadherin-secreting hybridoma cells in alginate-agar ose microcapsules. Hybridoma cells can be protected with biocompatible and semipermeable membranes that permit exit of anti-VE-cadherin monoclonal ant ibodies but not entry of cellular immune mediators. Stability studies were performed to select the suitable microcapsule for cell immobilization. Algi nate and agarose solid beads coated with poly-L-lysine and alginate were ch osen according to their stability and diusional properties. 1B5 hybridoma c ells were grown within the microcapsules and secreted anti-VE-cadherin anti bodies during the 9 days of culture, reaching a cumulative concentration of 1.7 mug/mL. This antibody concentration inhibited microtubule formation (8 7%) in the in vitro angiogenesis Matrigel assay. Moreover, the antiangiogen ic effect observed was antibody concentration related. These findings open a new alternative for the inhibition or prevention of angiogenesis and demo nstrates the feasibility of using microencapsulated cells as a control-drug delivery system. (C) 2001 John Wiley & Sons, Inc.