Secondary Lymphoid Tissue Chemokine as an Immunotherapeutic Against Primary and Metastatic Breast Cancer
Annual summary rept. 1 May 2004-30 Apr 2006
NEBRASKA UNIV MEDICAL CENTER OMAHA
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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 SLCCCL21 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 SLCCCL21 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 SLCCCL21. Sustained SLCCCL21 did not increase the length of survival when administered as an adjuvant immediately following tumor resection. However sustained SLCCCL21 delivery used as a neoadjuvant prior to tumor resection significantly increased the duration of survival. Our findings support further study of SLCCCL21 as a therapy for breast cancer one that may be capable of reducing residual and metastatic disease in breast cancer patients.
- Medicine and Medical Research