Phase I: It has become increasingly clear that the metastatic potential of solid cancer best correlates with the nature of the cells emigrating from the primary tumors. These emigrating cells enter the circulatory system and thus can readily be recovered using a simple and minimally invasive procedure. However, molecular analysis of these cells remains technically challenging because the emigrating metastatic tumor cells are few in number relative to the enormous numbers of normal blood cells, and because many of the tumor cells found in peripheral blood are dead or dying at any given moment. Current technology to detect tumor cells in peripheral blood involves a combination of cell size and density or positive- and negative-selecting immuno-enrichment steps. However, these protocols recover only a small fraction of the potentially available tumor cells, and the resulting cell populations are merely enriched, i.e., they are composed partially of non-tumor epithelial cells as well as dead and dying tumor cells. In Phase I, we propose to develop a clinically useful assay for the identification and isolation of circulating gastro-intestinal (GI) tumor cells by optimizing a novel cell separation technology. Our assay will use a cell adhesion matrix (CAM) to build a blood filtration unit that mimics the tumor intravascular microenvironment and thus will enable function-affinity purification of the circulating tumor cells. We anticipate the CAM enrichment will be able to accomplish a single step, one million-fold enrichment of viable human tumor cells from the peripheral blood of patients with late stage GI cancers. Flow cytometry, immunocytochemistry and real-time RT-PCR using cell lineage markers will be used to validate the CAM-recovered cells. The proposed Phase I study will measure the feasibility and efficiency of the CAM technology for use in the Phase II pathological study and molecular analysis of cancer cells in the blood. Ultimately, the combination of metastatic tumor cell enrichment and molecular targets acquired for specific GI cancers will create a technology that clinicians can use to establish staging, predict prognosis, and determine therapeutic responsiveness for multiple types of epithelial tumors.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Small Business Technology Transfer (STTR) Grants - Phase II (R42)
Project #
4R42CA108247-02
Application #
7017529
Study Section
Special Emphasis Panel (ZCA1-SRRB-C (J1))
Program Officer
Thurin, Magdalena
Project Start
2004-04-01
Project End
2008-03-31
Budget Start
2005-04-29
Budget End
2006-03-31
Support Year
2
Fiscal Year
2005
Total Cost
$682,437
Indirect Cost
Name
Vitatex, Inc.
Department
Type
DUNS #
095412081
City
Stony Brook
State
NY
Country
United States
Zip Code
11790