Materials to Engineer the Immune System

Abstract : The ex vivo manipulation of cells central to current approaches to cancer vaccines imposes a large economic and regulatory burden, dendritic cell modifications may be dependent on culture conditions and transient, and the vast majority of transplanted cells die following transplantation, leading to weak immune responses. The long-term objective is to bypass ex vivo cell manipulation in breast cancer vaccines, and instead develop effective material systems that program the immune system in situ. The specific hypothesis being addressed in this project is that a material system providing appropriate spatiotemporal presentation of GM-CSF, CpG oligonucleotides and specific tumor antigens to host dendritic cells (DCs) can effectively recruit, program and disperse host dendritic cells, and the programmed dendritic cells will be capable of stimulating specific T-cell populations and eliciting a strong anti-tumor response. In the previous funding cycle we demonstrated that polymers presenting appropriate cytokines and immunostimulatory cues can recruit large numbers of dendritic cells and regulate their activation. In this past year, we have demonstrated, in preliminary studies, that these polymeric vaccines can slow the progression of breast cancer growth, and reduce metastasis to the lungs.