The sensitive detection of low numbers of tumor cells in bone marrow and blood products (so-called """"""""micrometastases"""""""") in patients with a variety of sold-tumor malignancies is of extreme clinical significance. With existing technologies, the detection and characterization of micrometastases in problematic. Tumor cells exist in very low numbers in hematopoietic products, making sensitive detection difficult. Tumor detection assays, such as immunocytochemistry and PCR, are prone to problems with specificity. It is possible to improve both the sensitivity and specificity of micrometastases detection assays by increasing the number of analyzable tumor cells in the specimen. The project proposed here will develop a monoclonal antibody-based tumor enrichment column (TEC) for the selective capture of micrometastatic tumor cells from marrow and blood stem cell specimens from breast cancer patients. A model TEC will be developed using tumor cell-seeded specimens and hematopoietic products form breast cancer patients. A 3- log enrichment of tumor cells is anticipated. The development of such a tumor cell selection system will permit the rapid, sensitive, and specific enrichment of extremely low numbers of tumor cells. This advance will allow laboratory and clinical scientists to more sensitively and accurately detect, stage, and monitor patients' metastatic tumor burden.
The proposed research will result in a commercially available laboratory- scale column for the selective capture of viable breast cancer cells from hematopoietic products. This column will allow laboratory and clinical scientists to enrich the number of micrometastatic tumor cells in hematopoietic specimens. This will increase both the sensitivity and specificity of tumor detection diagnostic assays.
