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

摘要

T cells dendritic cells (DOs) and natural killer (NK) cells are known to be involved in anti-tumor immune responses. These cell types all express a common receptor CCR7 which binds the chemokine secondary lymphoid chemokine (SLC also called CCL21). 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 progress of human breast cancer. Utilizing this model we found that treatment of orthotopic tumors with sustained SLC/CCL21 delivery 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. Our studies in Task 2 have examined the effect of surgical resection of the primary tumor in combination with sustained SLC/CCL21. Sustained SLC/CCL21 did not increase the length of survival when administered as an adjuvant immediately following tumor resection. However sustained SLC/CCL21 delivery used as a neoadjuvant prior to tumor resection significantly increased the duration of survival. 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 in breast cancer patients.