BIOT 191 |
| A great deal of interest has surrounded the use of monoclonal antibodies (mAbs) for the selective delivery of cytotoxic agents to tumor cells. Although the approach is conceptually appealing, several limitations have been identified, including the physiological barriers to mAb extravasation and intratumoral penetration, conjugate immunogenicity, non-specific conjugate uptake, low drug potency, and inefficient release of active drug. Several of these limitations were overcome in developing mAb-valine-citrulline-MMAE (mAb-vc-MMAE) conjugates. These are comprised of the highly potent antimitotic agent monomethyl auristatin E (MMAE), attached to mAbs through a cathepsin B cleavable vc linker. This lecture will surround how this technology has been further optimized with newer generation drugs, linkers, and delivery agents. The results illustrate many of the key parameters in achieving high potency, pronounced therapeutic indices, bystander effects, and high intratumoral drug concentrations over sustained time periods. An overview of this therapeutic approach to cancer therapy will be provided. |
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Biophysical and Biomolecular Symposium: Targeted Delivery of Proteins & Nucleotides
8:00 AM-11:00 AM, Wednesday, August 22, 2007 BCEC -- 107 A/B, Oral
Division of Biochemical Technology |