(417f) Cell-Free, Dendritic Cell-Mimicking Vaccines for Cancer, COVID-19, and Beyond

Vaccines are acknowledged as one of the indispensable means for human health, especially during the COVID-19 pandemic. Traditional vaccines are effective and reliable, but vaccines against many infectious and non-infectious diseases are still in great demand. A key orchestrator in the adaptive immune system is dendritic cells (DCs), antigen presenting cells that prime T cells for directed cellular and humoral immunity. DC-based vaccines avoid many hurdles of administration, circulation, uptake by APCs, intracellular antigen processing, and antigen presentation along with stimulatory signals, resulting in orders of magnitude improved vaccination efficacy while lowering side effects. However, DC-based vaccines also offer limitations of physical and biological stability, adaption to suppressive environment, and specific storage and handling requirements. In order to overcome the shortcomings, DCs were chemically converted to acellular vesicles that still preserve most characterizations and functions of DCs, called extracellular blebs (EBs). DC-EBs are structurally and functionally homogenous after produced by fast, simple, and highly scalable processes. They also demonstrated stable antigen presentation to T cells with maturation-dependent tunable stimulation. DC-EBs loaded with a tumor-specific peptide effectively eradicated target tumor cells in vitro and in vivo by generating cytotoxic T lymphocytes (CTLs). EBs derived from DCs genetically engineered to express SARS-CoV-2 spike proteins were able to generate antibodies in vivo that effectively neutralized SARS-CoV-2. EBs are cell-derived materials that allow engineering a broad range of cells to tunable, biologically safe, easy handled, and diverse therapies including vaccines, as an example in this study, and beyond.