Abstract

This project will examine the use of a three component pre-targeting radioimmunotherapy (PRIT) strategy in breast cancer animal models and patients with metastatic breast cancer. The three components include a novel recombinant fusion protein composed of four single chain antibodies and streptavidin (sFv4/SA) which will target breast cancer tumor-associated antigens (TAG-72 and MUC-1). The second component is a synthetic clearing agent which produces rapid hepatic clearance of circulating sFv4/SA prior to administration of the third component, Biotin-DOTA-isotope carrying imaging and therapeutic isotopes. The isotope delivery system as a low m.w. (0.9 kD) with rapid distribution throughout the body for tumor localization and rapid urinary excretion. This strategy has a 10-fld increase in tumor to normal tissue ratios as compared to radiolabeled antibodies. We will carry out a series of studies in breast cancer animal models to optimize therapy variables, explore several therapeutic isotopes and examine therapeutic efficacy and several sites of metastases. Human trials will include phase I and II trials of CC49 sFv4/SA followed by Biotin-DOTA-111In/90Y as well as subsequent trials derived from the animal model studies. These studies are to be done in collaboration with NeoRx, Inc.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Specialized Center (P50)
Project #
1P50CA089019-01
Application #
6403857
Study Section
Special Emphasis Panel (ZCA1)
Project Start
2000-09-30
Project End
2005-09-30
Budget Start
Budget End
Support Year
1
Fiscal Year
2000
Total Cost
Indirect Cost

  Institution

Name
University of Alabama Birmingham
Department
Type
DUNS #
004514360
City
Birmingham
State
AL
Country
United States
Zip Code
35294

  Publications

Wielgos, Monica E; Zhang, Zhuo; Rajbhandari, Rajani et al. (2018) Trastuzumab-Resistant HER2+ Breast Cancer Cells Retain Sensitivity to Poly (ADP-Ribose) Polymerase (PARP) Inhibition. Mol Cancer Ther 17:921-930
Wielgos, Monica E; Rajbhandari, Rajani; Cooper, Tiffiny S et al. (2017) Let-7 Status Is Crucial for PARP1 Expression in HER2-Overexpressing Breast Tumors. Mol Cancer Res 15:340-347
Forero, Andres; Li, Yufeng; Chen, Dongquan et al. (2016) Expression of the MHC Class II Pathway in Triple-Negative Breast Cancer Tumor Cells Is Associated with a Good Prognosis and Infiltrating Lymphocytes. Cancer Immunol Res 4:390-9
McNally, Lacey R; Mezera, Megan; Morgan, Desiree E et al. (2016) Current and Emerging Clinical Applications of Multispectral Optoacoustic Tomography (MSOT) in Oncology. Clin Cancer Res 22:3432-9
Atherton, Daniel S; Sexton, Katherine C; Otali, Dennis et al. (2016) Factors Affecting the Use of Human Tissues in Biomedical Research: Implications in the Design and Operation of a Biorepository. Methods Mol Biol 1381:1-38
Li, Rong; Zhang, Kui; Penedo, Thuy Linh et al. (2016) The RANK Pathway in Advanced Breast Cancer: Does Src Play a Role? Appl Immunohistochem Mol Morphol 24:42-50
Walters, Beth; Thompson, Sunnie R (2016) Cap-Independent Translational Control of Carcinogenesis. Front Oncol 6:128
Wu, Lizhi; Chaudhary, Sandeep C; Atigadda, Venkatram R et al. (2016) Retinoid X Receptor Agonists Upregulate Genes Responsible for the Biosynthesis of All-Trans-Retinoic Acid in Human Epidermis. PLoS One 11:e0153556
Otali, D; Fredenburgh, J; Oelschlager, D K et al. (2016) A standard tissue as a control for histochemical and immunohistochemical staining. Biotech Histochem 91:309-26
Hoyt, Kenneth; Umphrey, Heidi; Lockhart, Mark et al. (2015) Ultrasound imaging of breast tumor perfusion and neovascular morphology. Ultrasound Med Biol 41:2292-302

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