Novel Approaches To Target The Immune System In Gastrointestinal Cancers PDF Download

Many kinds of cancer, and almost universally metastatic cancer, are refractory to treatment by conventional methods: surgery radiation, and non-specific cytotoxic chemotherapy. The dawn of the age of personalized medicine presaged 15 years ago with the completion of the human genome project has thus far largely failed to deliver on the promise of targeted therapeutics. We have recently seen the development of immunotherapy as a compliment to these methods. Immunotherapies hold an advantage in that they are not specific to driver mutations or oncogenic pathways that may change, but recognize an array of tumors antigens and can adapt over time to the emergence of new tumor cell populations with new characteristic mutations and antigens. In order to achieve systemic long-lasting anti-tumor immunity, immunosuppression in the tumor microenvironment must be overcome. We have developed technologies to accomplish this through the targeting and activation of immunosuppressive innate leukocytes that without treatment would otherwise promote tumor survival, growth, and metastasis, and inhibit the establishment of tumor-specific immunity. We have utilized an attenuated strain of Listeria monocytogenes and the self-assembling eCPMV viral-like nanoparticle. These two immunotherapies target innate leukocytes in the tumor microenvironment and induce their production of pro-inflammatory cytokines and chemokines that recruit in new effector cell subsets. Listeria and eCPMV show clear efficacy in mouse models of melanoma, ovarian carcinoma, colon cancer, and breast carcinoma. Our results highlight the value in emerging therapeutic strategies that target immunosuppressive innate immune cells in the tumor microenvironment.