Abstract 2816: Immune-tolerant elastin-like polypeptide (iTEP) particles promote peptide vaccine presentation by dendritic cells

Abstract

Abstract T cell epitope-based peptide vaccines are promising experimental therapeutics for cancer and infection due to their unparalleled specificity, yet their presentations by dendritic cells (DCs) are hindered by their intrinsic limitations: short half-lives, non-typical antigen sizes for DCs to take in and process, lack of intrinsic adjuvants, and poor cross-presentation efficiencies. We aimed to boost the presentation by fabricating an immune-tolerant elastin-like polypeptide (iTEP) nanoparticle (NP) to resolve the limitations. The properties of iTEPs that render them as ideal vaccine carriers include their non-immunogenic and non-inflammatory natures, their simple purification method through phase transition, and their ability to fuse the vaccines and peptide adjuvants together. We first fused a cytotoxic T lymphocyte (CTL) epitope vaccine, SIINFEKL, from ovalbumin to an iTEP amphiphilie and found the fusion is able to self-assemble into NPs. The NP was turned into a size similar to virus-like particles by modulating the iTEP sequences. The NP enhanced the presentation of SIINFEKL with H2b on the surface of DC2.4 cells in comparison with free peptide, ovalbumin, or soluble vaccine-iTEP fusions. Interestingly, another iTEP-vaccine fusion which forms larger, micrometer-sized aggregates led to even stronger vaccine presentation, an observation still under investigation. Moreover, our preliminary data showed that co-delivering the vaccines and an adjuvant peptide from flagellin by iTEPs also augmented the peptide vaccine presentation. Lastly, the iTEP NPs that deliver tumor antigen Kras- and hTERT-derived peptide vaccines were also generated and are currently under study with a hope to improve the efficacy of these vaccines. In summary, iTEP particles enhanced peptide vaccine presentation. The underlying mechanisms of the enhancing effects of iTEP particles on the vaccine presentation will be studied next. Supported by the University of Utah Start-up fund and the University of Utah SEED grant Citation Format: Mingnan Chen, Shuyun Dong, Scott Cho. Immune-tolerant elastin-like polypeptide (iTEP) particles promote peptide vaccine presentation by dendritic cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2816. doi:10.1158/1538-7445.AM2014-2816