Immunomodulation

Surgery, radiation, and chemotherapy have been the primary options for cancer patients; however, the recent emergence of immunotherapy has revolutionized the cancer treatment paradigm. Cancer immunotherapies employ a patient’s immune system to recognize and fight cancer, but recruiting immune cells to tumors specifically and in adequate numbers is a significant challenge.

In order to address this obstacle, we propose to employ lysolipid-containing liposomes (LTSLs) for delivering chemokines, signaling proteins which induce cell migration, to the tumor microenvironment.  While the liposomes are designed to slowly elute contents over hours, complete release can be achieved within minutes upon heating.  Thus, the nanocarrier may be used for local release of chemokine within solid tumors as a strategy to recruit lymphocytes.  We are particularly interested in recruiting B1 lymphocytes due to their stimulatory impact on multiple antitumor immunological processes. For instance, these cells have been shown to produce tumor-specific IgM antibodies which can promote cancer cell death. Additionally, B1 lymphocytes are able to enhance T cell-mediated antitumor immune response by expressing two co-stimulatory signals, CD80 and CD86, for T cell activation. B1 lymphocytes have demonstrated the ability to phagocytose apoptotic cells which can help to reduce inflammation, a process that promotes tumor progression mechanism. We hypothesize that the recruitment of B1 lymphocytes to the tumor site, through the utilization of chemokine-loaded TSLs, will bolster and lead to a more effective an antitumor immune response.