UC San Diego

Advancement in the understanding of tumor immunology has led to the development of novel therapies that can augment endogenous immunity and elicit potent antitumor immune responses. Concurrently, nanomedicine has revolutionized the way we fight diseases with unique physical properties and distinct mechanisms of action. In particular, cell membrane-coated nanoparticles, which are biomimetic nanotherapeutics derived from natural plasma cell membrane, have demonstrated tremendous benefits in cancer immunotherapy.Herein, the first chapter of this dissertation will be dedicated to the design principles and current status of cancer cell membrane-coated nanoparticles for anticancer vaccination. The second chapter of the dissertation will focus on the design, fabrication, and biological functions of a biomimetic anticancer vaccine that can co-deliver tumor antigens and immunostimulatory adjuvants. This nanovaccine utilizes natural cancer cell membrane to provide multivalent-antigen specificity, drains efficiently to lymphatic system to engage immune cells, and elicits a strong immune response to control tumor growth in both prophylactic and therapeutic settings. The third chapter of the dissertation will focus on the design, fabrication, and biological functions of a biomimetic nanoparticle platform that can be used to mobilize specific T cell subsets without the need for professional antigen-presenting cells. This nanoparticle utilizes engineered cancer cell membrane that express a T cell co-stimulatory marker and present peptide epitopes, the two signals necessary to promote tumor antigen-specific T cell immune responses. These two platforms both represent powerful tools that can be used to develop personalized cancer immunotherapies down the road. This dissertation will serve as a paradigm to rationally design both natural and engineered cancer cell membrane coated nanoparticles for antitumor immunotherapy. By harnessing the amply available engineering tools, researchers could enhance the functionalities of cell membrane beyond the natural properties of parent cells, and significantly expand the application of cell membrane-coated nanoparticles beyond antitumor immunotherapy.