Radiolabeled Herceptin to Increase Treatment Efficacy in Breast Cancer Patients With Low Tumor HER-2/neu Expression
Abstract
The primary objective of the proposal is to evaluate the efficacy and feasibility of using radiolabeled Herceptin antibody to target rapidly accessible breast carcinoma cells or micrometastases. By using Herceptin to specifically deliver radiation we anticipate that the efficacy of Herceptin will be extended to include breast cancer cells that are not high HER-2/neu antigen expressors. This hypothesis will be tested using the spheroid model to simulate rapidly accessible micrometastases. An alpha-particle emitting radionuclide will be used to enhance tumor cell kill. Spheroids of 3 breast carcinoma cell lines exhibiting, high, intermediate and low expression of HER-2/neu have been generated and characterized (task 1). Antibody penetration by confocal microscopy has been measured for these 3 spheroids and an appropriate Herceptin concentration has been chosen for cell kill experiments (task 2). Preliminary cell kill experiments using Herceptin labeled with an alpha-particle emitter have been carried out; dose-response studies have been started and are on going (task 3: month 7-20) . Preliminary results suggest that alpha-emitter labeled Herceptin will be effective against tumor cells that have a 3 to 4-fold lower expression of HER/neu.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2001
- Accession Number
- ADA396696
Entities
People
- George Sgouros
Organizations
- Memorial Sloan Kettering Cancer Center