Abstract
Abstract Immunotherapy has shown promise in cancer treatment but achieved limited success in clinic trials. With this strategy, eliciting strong antitumor immune response in vivo remains a challenge, largely due to the immunosuppressive tumor microenvironment and inefficient delivery of cancer vaccine. Nanoparticle-delivered antigen together with adjuvants provides a promising strategy to increase the vaccine delivery efficiency. Recently, our group developed a multi-stage silicon vector (MSV) system for protected and prolonged nano-scale drug delivery. MSV delivered siRNA in vivo induced sustained knockdown of target gene expression and subsequent anti-tumor efficacy in mice. Here we tested the effect of MSV-formulated antigen peptides and Toll-like receptor (TLR) ligands on dendritic cells. By formulating HER-2 antigen peptide together with TLR4 ligand (MPLA) and TLR9 ligand (CpG), we found that MSV-delivered antigen and TLR ligands were uptaken by mouse dendritic cells after 1h co-incubation, and started to be released inside the cells at 3 h after co-incubation. Moreover, MSV-delivered TLR ligands strongly activated mouse dendritic cell expression of co-stimulatory molecules such as CD80 and CD86. It also induced dendritic cells to produce large amount of pro-inflammatory cytokines, such as TNF-alpha, IL-6, and IL-12. In summary, MSV-delivered vaccine efficiently delivered antigen and immuno-activating TLR ligands together into dendritic cells, and promoted dendritic cell maturation and activation. Therefore, MSV formulation of tumor antigen and TLR ligands may serve as a nano-scale cancer vaccine with enhanced in vivo efficacy. Ongoing experiments include testing in vivo T cell responses to MSV-delivered HER-2 antigen peptide and TLR ligands, and determining the antitumor efficacy on mouse mammary gland tumor model. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1967. doi:1538-7445.AM2012-1967
Published Version
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