Secondary Lymphoid Tissue Chemokine as an Immunotherapeutic Against Primary and Metastatic Breast Cancer

Abstract : To generate anti-tumor immune responses, T cells must interact with mature dendritic cells (DCs) presenting tumor-derived peptides. Natural killer (NK) cells, DCs, and T cells express a common receptor, CCR7, which binds the chemokine SLC/CCL21. SLC/CCL21 is normally expressed in the lymphoid organs and coordinates the interactions between DCs and T cells, thus initiating T cell responses. In Task 1, we examined the effect of SLC/CCL21 administered via a sustained delivery system in a mouse breast cancer model that mirrors the progression of the human disease. Utilizing this model, we found that treatment of orthotopic tumors with sustained SLC/CCL21 resulted in primary tumor growth inhibition and significantly reduced spontaneous lung metastases. Examination of tumor-infiltrating leukocytes by flow cytometry revealed this treatment increased NK cells and CD8+ T cells. Current studies in Task 2 are examining if the resection of the primary tumor. in combination with sustained SLC/CCL21 given before or concurrent with resection will potentiate the therapeutic effects observed in Task 1. Our findings support further study of SLC/CCL21 as a therapy for breast cancer, one that may be capable of reducing residual and metastatic disease, and therefore a promising treatment for breast cancer patients.