Abstract 1565: Mesoporous silicon particle mediated dendritic cell based vaccine formulation showed stronger immunoresponse for the presentation of tumor antigens and adjuvant

Abstract

Abstract Dendritic cell (DC) based immunotherapy is being used for cancer therapy in various clinical trials. During evaluation of recent clinical studies, it became apparent that efficient DC-based immunotherapy is dependent on a number of factors, such as the mode of antigen presentation, maturation of DC, injection site, and vaccination dosing. Major limiting factors for DC-based vaccines are insufficient loading of antigens by DC and poor migratory capacity of DC to lymph nodes. Nanotechnology provides tools to load large payloads of antigens and adjuvants in particles for uptake by DC. Toll-like receptor (TLR) ligands have been proposed as vaccine adjuvants for boosting adaptive immunity in cancer therapy. TLR signaling induces DC activation that is characterized by enhanced expression of costimulatory molecules and increased secretion of cytokines necessary for activation and differentiation of naive T cells. In this study, we have used porous silicon (pSi) microparticles to create a novel vaccine. We have demonstrated that porous silicon particles can be decorated with TLR-ligands using lipopolysaccharide (LPS) or monophosphoryl lipid (MPL). This decorated particles are substrates for bone marrow-derived DC internalization, leading to cellular uptake and activation and enhanced migration of DC to lymph nodes. Confocal and scanning electron microscopy, as well as flow cytometry studies supported higher uptake of LPS and MPL conjugated particles as compared to unlabeled particles. TLR ligands induced morphological changes in GM-CSF-stimulated bone marrow cells during particle uptake consistent with classical DC dentron formation. Stimulated antigen presenting cells also expressed elevated levels of costimulatory (e.g. CD80, CD86) and major histocompatibility molecules (MHC), and secreted pro-inflammatory cytokines both in vitro and in vivo. Ex-vivo processed DC loaded with TLR ligand coated pSi showed enhanced migration to lymph node as compared with empty DC when injected mice subcutaneously. As expected, LPS conjugation to particles showed toxicity towards DC whereas MPL conjugated pSi showed little or no toxicity. 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 1565. doi:1538-7445.AM2012-1565