Exploring the Use of Virally-Delivered Therapeutic Genes to Inhibit Breast Cancer Tumor Growth and Unleash Immune Responses

Danuta Kozbor, PhD

Progression of breast cancer is intimately related to a network of interactions of neoplastic epithelial cells with the surrounding tumor stroma, which is a mixture of hematopoietic, endothelial and mesenchymal cells producing stromal-derived factors that promote tumor growth.  The CXCR4 receptor for the CXCL12 chemokine is involved in these signaling interactions between tumor cells and their microenvironment and plays a pivotal role in establishing metastasis by attracting suppressive elements from bone marrow to the tumor microenvironment (TME).  

For these reasons, inhibition of the CXCL12/CXCR4 signaling axis is expected to affect a broad range of antitumor processes leading to inhibition of tumor growth and dissemination.  

Dr.  Danuta Kozbor is leading research funded by donations to Roswell Park to determine whether blocking the CXCL12/CXCR4 ligand/receptor signaling pathway would inhibit breast cancer metastases and unleash immune responses against the tumor.  Her approach uses an oncolytic vaccinia virus (OVV), which replicates in and destroys cancer cells selectively, to deliver an antagonist of the CXCR4 receptor directly to the microenvironment of breast carcinomas in lab models.

It is anticipated that results of this study will have a significant impact on treatment in patients with triple-negative breast tumors.