Anti-NCL Immunoagent for Cancer Diagnosis and Therapy
T2015-281 Nucleolin (NCL) is up-regulated in cancer cells, and modulates pro-tumorigenic pathways and chemoresistance. This anti-NCL agent binds and blocks NCL signaling, and may be optimized as cancer therapeutic and diagnostic tool.
Despite huge advancements in detection and treatment, cancer remains a top world health concern. One of the major limitations of current technology is adequately detecting tumor margins and micrometastases. Even with aggressive tumor resection and adjuvant chemotherapy or radiotherapy, tumor cells often remain at the primary site or elsewhere in the body. Nucleolin (NCL) is one of the most abundant non-ribosomal proteins in the nucleolus, first identified in ribosomal RNA processing. NCL is frequently up-regulated in cancer and cancer-associated endothelial cells compared to normal tissues, where it is also present on the cell surface. Because of its oncogenic role and specific expression on cancer cells surface, NCL represents an attractive target for anti-neoplastic therapies. Several groups have attempted to develop molecules to bind and to inhibit NCL in cancer cells. These compounds have also been suggested as potential carriers for the targeted delivery into cancer cells of several anti-neoplastic agents. Although promising, other agents targeting NCL suffer from intrinsic limitations, such as extremely short half-life, undesired immunostimulatory actions, and still unknown toxicological effects.
To overcome some of these limitations, Dr. Croce and his team at The Ohio State University have developed a novel immunoagent that is capable of binding nucleolin (NCL), an abundant protein that is up-regulated on the surface of cancer cells. This agent presents value as a cancer treatment -- it has been shown to be anti-neoplastic in vitro and in vivo for breast cancer; additionally, treatment compounds (chemotherapeutic pro-drugs, radioactive therapeutics) can be joined to the molecule and targeted to cancer cells to potentially improve its efficacy. Furthermore, fluorescent- or radioactive-labeling can be added to this immunoagent to permit better imaging of tumor margins and metastatic lesions in patients
- Significant ability to discriminate between cancer and normal cells.
- Targeted treatment potential
- Fluorescent- or radioactive-labeling for surgery planning and assessment of tumor removal