Physiopathology of chemokine receptor interactions

Tumor expression of a chemokine receptor directs metastasis preferentially to the organs in which the chemokine ligand is secreted, suggesting chemokine receptors as promising therapeutic targets.  Our main research interest is to determine how chemokines and chemokine receptors participate in the control of tumor growth and progression, and to evaluate their potential as antitumor targets.

The chemokine receptor CCR9 is expressed primarily on thymocytes and in a small subset of intraepithelial lymphocytes.  Its overexpression increases the migratory and invasive capacity of prostate cancer cells, directs ovarian cancer and melanoma metastases to the small intestine, and activates anti-apoptotic pathways that lead to survival and increased proliferation of leukemia cell lines.

Our group has generated and characterized anti-human CCR9 monoclonal antibodies that reduced human T lymphoblastic cell tumors transplanted into mice by >85%.  Tumor size reduction was concomitant with an increase in the fraction of apoptotic tumor cells and in tumor necrotic areas, as well as a decrease in the fraction of proliferating cells and in tumor vascularization.  We are interested in the characterization of specificity, affinity and mode of action of these antibodies.  In addition, we are studying whether CCR9-expressing tumors such as acute T cell lineage leukemia might be targeted with these antibodies.