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 to deliver cytotoxic payloads to breast cancer stromal fibroblasts. The central hypothesis to be tested is that targeting the breast cancer stroma will result in enhanced tumor cytotoxicity compared to targeting the breast cancer cells themselves. Fibroblasts activation protein (FAP) is a cell surface glycoprotein selectively expressed by tumor stromal fibroblasts in breast tumors, but not significantly expressed by breast cancer cells, normal fibroblasts, or other normal tissues. We have identified an appropriate animal model that allows for evaluation of both stromal and epithelial targeting using BT-474 xenografts. In multiple biodistribution experiments using I(exp 125) radiolabeled antibodies targeting either HER2 or FAP, epithelial targeting was accomplished. However, stromal targeting of FAP remains suboptimal, most likely due to the relatively low copy number of FAP in the tumor stroma compared to tumor antigens. Although targeting the tumor stroma was challenging utilizing the antibody reagents tested in this proposal, additional antibody reagents are under development including higher affinity antibodies to overcome the challenges encountered. The biodistribution experiments conducted can inform future therapeutic studies to investigate a radioimmunotherapeutic strategy for treatment of breast cancers.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2006
- Accession Number
- ADA462144
Entities
People
- Jonathan D. Cheng
Organizations
- Fox Chase Cancer Center