Dendritic cells-targeted nano-vaccines sensitize melanoma to immune checkpoint modulators

Despite the remarkable efficiency of immune checkpoint modulators against metastatic melanoma, there is a low percentage of responders and clinical trials report severe immune-mediated side effects and disease relapse. Recent evidences show that non-tumor cells within the tumor microenvironment (TME), including tumor vasculature and immune stromal cells, dictate the overall therapeutic efficacy. We synthesized an off-the-shelf and cost-effective nano-sized polymeric platform that combines a cancer vaccine with the targeted inhibition of molecular and/or cellular immune suppressive players. These precision nano-sized medicines aim to re-educate and harness patient T-cell response against tumors, leading to an immunological memory able to control tumor relapse without any follow-up treatment. The design of these advanced peptide and RNA immunotherapeutics is guided by the identification of lead immune suppressor factors and tumor specific antigens using novel 3D bio-printed tumor-immune spheroids developed in our lab. Our first nano-immunotherapy candidates sensitized melanoma mouse models to immune-checkpoint modulators, dramatically increasing disease-free survival rates.