Radioimmunotherapeutic Targeting of Breast Cancer Stroma
Abstract
The objective of this proposal is to determine the effectiveness of tumor stromal targeting using radio-labeled antibodies that deliver cytotoxic payloads to breast cancer stromal fibroblasts expressing fibroblast activation protein (FAP). The central hypothesis to be tested is that targeting breast cancer stroma will result in enhanced tumor cytotoxicity compared to targeting the breast cancer cells themselves. FAP is a fibroblast cell surface glycoprotein that is selectively expressed by tumor stromal fibroblasts in breast tumors, but is not significantly expressed by breast cancer cells, normal fibroblasts, or other normal tissues. The authors have identified an appropriate animal model that allows for evaluation of both stromal and epithelial targeting of BT-474 xenografts. Although epithelial targeting was accomplished, stromal targeting of FAP remains under development utilizing additional antibody reagents. These initial biodistribution studies will inform future therapeutic studies to investigate a radioimmunotherapeutic strategy for preclinical treatment of breast cancers in an animal model. If a radioimmunotherapy strategy is effective in inhibiting breast cancer growth in an animal model, it may lead to a novel therapeutic approach targeting the tumor stroma in patients with breast cancer.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2005
- Accession Number
- ADA447606
Entities
People
- Jonathan D. Cheng
Organizations
- Fox Chase Cancer Center