(396h) Chemokine Releasing Polymer Implants to Direct Immune Cell Migration in the Setting of Colon Cancer
Colorectal cancer (CRC) is the third leading cause of cancer related death in both men and women. The major cause of death is metastasis and frequently, the target organ is the liver. Successful metastasis depends on a microenvironment conducive to seeding and colonization by metastatic cells. Inflammatory immune cells are implicated in the formation of this microenvironment and interfering with current treatment options including chemotherapy. The objective of the current work is to control immune cell migration and accumulation in vivo, directing these cells away from target organs for metastatic disease. In an orthotopic model of colon cancer in which CT26 cells are injected into the cecum, liver metastasis occurs in 90% of mice. Histological analysis indicated that immune cells accumulate within the liver prior to the arrival of metastatic cells. Microarray analysis of pre-metastatic livers from mice injected with CT26 cells indicated that inflammatory chemokines CXCL1 and CCL6 were increased 5.6 and 6.3 fold, compared to mice receiving saline injection. This presentation will focus on the development of biocompatible polymer implants designed for sustained release of these chemokines from the subscapular space, a site where immune cells do not generally accumulate and colon cancer metastasis does not occur. We will discuss the ability of these implants to attract immune cells expressing CXCR2 and CCR1, prototypical receptors for CXCL1 and CCL6, respectively. We will identify the immune cell populations that reside within the implant site and report their numbers in the pre-metastatic liver and primary tumor in mice with and without polymer implant. Finally, the efficacy of these immunomodulatory implants to decrease liver metastatic load will be presented. Collectively, we expect the outcome of this work to impact our understanding of the underlying immunological mechanisms that promote metastatic cancer and aide in the efforts to treat it.