Probing Tumor Microenvironment with In Vivo Phage Display
Annual rept. 1 Jul 2012-30 Jun 2013
SANFORD-BURNHAM MEDICAL RESEARCH INST LA JOLLA CA
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The purpose of this study is to develop specific probes that target various cells populations in the tumor microenvironment. Tumor stroma contains many cell populations, such as vascular endothelial cells, immune cells, mesenchymal cells, and extracellular matrix, which are critical to tumor development and progression. Although various probes have been developed for tumor vasculature, there is a scarcity of markers for tumor macrophages, fibroblasts, nerve cells and the matrix. The goal of our group is to make technical improvements in our phage display system, and find peptides that target carcinoma-associated fibroblasts CAFs in breast tumors. To reach the goal, we have improved our phage display technology by involving in the screens iRGD, a tumor-specific tissue-penetrating peptide. iRGD enhanced the penetration of co-applied phage libraries into breast tumor tissue by two fold, allowing the libraries to reach and probe the stromal compartments within the tumors. We have also optimized high throughput sequencing for phage DNA, and methods to isolate CAFs from breast tumor tissue. Multiple phage library screens are underway. In parallel, we have made an unexpected discovery that iRGD itself is an efficient CAF-targeting peptide, and that the iRGD receptor neuropilin-1 is a potential CAF marker in breast tumors. iRGD in combination with novel CAF-targeting peptides may result in an efficient probe for breast tumor imaging and therapy.
- Medicine and Medical Research