Breast cancer immunotherapy has improved outcomes for some patients, but most, especially those with triple-negative breast cancer (TNBC), still do not benefit from current checkpoint inhibitors. This project builds on promising early findings for SSFF-02, a chemokine receptor inhibitor that reduced tumor growth and metastasis in two TNBC mouse models without observable toxicity. Because chemokines help control immune cell movement and tumor spread, blocking multiple chemokine pathways at once may offer a new strategy for treating advanced disease. The study advances two goals. First, it will test SSFF-02 in combination with anti-programmed cell death protein 1 (PD-1) immunotherapy in advanced breast cancer mouse models to determine whether dual treatment improves antitumor immune response and reduces metastasis. Second, it will develop new hypoxia-targeted versions of SSFF-02 using artificial intelligence–assisted drug design tools available through the UTEP Core Facility. These next-generation compounds are intended to work more effectively in the low-oxygen regions of breast tumors where standard therapies often fail. The project is designed to generate preclinical evidence for a new class of small-molecule immunomodulators with potential to improve treatment access and reduce cost-related disparities in breast cancer care.