We are developing methods for in situ vaccination against cancer and are exploring multiple approaches. We have reported on the development of unimicellar hyperstar macromolecular chimeras displaying multiple peptide antigens, prepared <i>via</i> a combination of click chemistry and esterification reactions starting from a biodegradable hyperbranched polymer template. Hyperstars were solubilized in aqueous solution to provide a multi-antigen unimicellar cancer nanovaccine of about 20 nm. We have recently extended this approach to provide a scaffold for the display of up to 512 antigens. Sequential strain promoted azide-alkyne click (SPAAC) conjugation was applied for peptides CLEC9A (dendritic cell targeting), GP100 (melanoma antigen), TRP2 (melanoma antigen) and PADRE (T-helper peptide). We combine the vaccine with TLR immune adjuvants and will review the in vitro and in vivo efficacy of the resulting vaccines. Further, the efficacy will be compared with approaches to encapsulate agonists within the core of lipid carriers and methods to release tumor antigen through focal ablation.

Engineering personalized peptide-based cancer nanovaccines

2019 Fall National Meeting

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