Ameya Kirtane, PhD

Melanoma patients who do not respond to immunotherapies will benefit significantly if these therapies are combined with cancer vaccines. An ideal cancer vaccine should contain adjuvants that deliver the antigen to dendritic cells and stimulate them to produce a CD8+T cell response. Unfortunately, most adjuvants perform only one of these functions, often suboptimally. Hence, there is a critical need for adjuvants that deliver tumor antigens intracellularly and activate dendritic cells. Delivering antigens adsorbed on nanoparticles enables intracellular delivery. Moreover, the materials used in some nanoparticles can activate dendritic cells, though what material properties are required for such activation remains unclear. To generate an effective cancer vaccine, this project will synthesize a library of nanoparticles from >300 novel polymers. The project will measure their ability to deliver antigen and activate dendritic cells using high throughput flow cytometry. Finally, it will test the anticancer efficacy of lead vaccines in combination with FDA approved immunotherapies in a mouse melanoma model. Completion of this work will help identify a vaccine for melanoma. Additionally, multi-parametric data obtained from the screens will help establish a structure-function relationship between polymers and dendritic cell activation, providing critical information for future vaccine development.