Microfluidic engineering of immunogenic exosomes for personalized cancer vaccine
Prof. Mei He, Department of Biological & Agricultural Engineering
Kansas State University
Project dates: 2016-2017
Exosome, as a natural and safe therapeutic delivery system, is emerging in cancer immunotherapy, yet hard to harvest as a pure, immunogenic population. Consequently, co-purified exosome subtypes and extracellular microvesicles could confound our understanding on activation of immune pathways and effective cancer vaccination. This project specifically addresses technology challenges by introducing a lowcost microfluidic approach for large-scale production of clinical-grade immunogenic exosomes, and examining the roles of immunogenic exosomes in MHC-I antigen presentation pathway and antitumor responses. The study focuses on the immunogenicity of peptide-engineered exosomes in antitumor responses. The long term goal is to establish an enabling strategy for studying immunogenic roles of variable peptide-engineered exosomes in cancer immunotherapy and developing personalized cancer vaccines. Microfluidic high-throughput isolation of MHC-I specific exosomes will be uniquely streamlined with vesicular loading of antigenic peptides, and subsequent light-triggered release of intact, engineered exosomes in continuous-flow. The engineered immunogenic exosomes will be assessed to the degree of potency and activity in stimulating immune pathways that are critical for an effective antitumor response in vitro (e.g., CD8+ cytotoxic T cells and CD4+ T helper cells stimulating). Outcomes will increase understanding of fundamentals and roles of variable peptide-pulsed immunogenic exosomes in immune system, provide well defined models for in vivo study of immunogenic exosomes in tumor microenvironment, and gain knowledge of cell-free cancer vaccination system for designing personalized cancer vaccines.