TLR Agonist Nano Immune Therapy Clears Peritoneal and Systemic Ovarian Cancer.

Intraperitoneal (IP) administration of immunogenic mesoporous silica nanoparticles (iMSN) in a mouse model of metastatic ovarian cancer promotes the development of tumor-specific CD8 T cells and protective immunity. IP delivery of iMSN functionalized with the Toll-like receptor (TLR) agonists polyethyleneimine (PEI), CpG oligonucleotide, and monophosphoryl lipid A (MPLA) stimulated rapid uptake by all peritoneal myeloid subsets. Myeloid cells quickly transported iMSN to milky spots and fat-associated lymphoid clusters (FALCs) present in tumor-burdened adipose tissues, leading to a reduction in suppressive T cells and an increase in activated memory T cells.

Intercellular Communication Through Microtubular Highways.

Tunneling nanotubes (TNTs) are open-ended, membrane-encased extensions that connect neighboring cells. They have diameters up to 1 μm but are able to expand to convey large cargos. Lengths vary depending on the distance of the cells but have been reported to be capable of extending beyond 300 μm.

Cancer Cell Silicification and Surface Functionalization to Create Microbial Mimetic Cancer Vaccines.

As cancer progresses, tumor cells adapt to evade immune cells. To counter this, cancer cells can be silicified ex vivo, creating surface masks that can be decorated with microbial-associated molecules that are readily recognized by antigen-presenting cells (APCs). The transformation process renders the tumor cells nonviable and preserves the integrity of the cell and associated tumor antigens.

Specific Tumor Localization of Immunogenic Lipid-Coated Mesoporous Silica Nanoparticles following Intraperitoneal Administration in a Mouse Model of Serous Epithelial Ovarian Cancer.

Immunogenic lipid-coated mesoporous silica nanoparticles (ILM) present pathogen-associated molecular patterns (PAMPs) on the nanoparticle surface to engage pathogen-associated receptors on immune cells. The mesoporous core is capable of loading additional immunogens, antigens or drugs. In this study, the impact of lipid composition, surface potential and intercalation of lipophilic monophosphoryl lipid A (MPL-A) in the lipid coat on nanoparticle properties and cellular interactions is presented.

Monitoring Therapeutic Responses to Silicified Cancer Cell Immunotherapy Using PET/MRI in a Mouse Model of Disseminated Ovarian Cancer.

Current imaging approaches used to monitor tumor progression can lack the ability to distinguish true progression from pseudoprogression. Simultaneous metabolic 2-deoxy-2-[F]fluoro-D-glucose ([F]FDG) positron emission tomography (PET) and magnetic resonance imaging (MRI) offers new opportunities to overcome this challenge by refining tumor identification and monitoring therapeutic responses to cancer immunotherapy. In the current work, spatial and quantitative analysis of tumor burden were performed using simultaneous [F]FDG-PET/MRI to monitor therapeutic responses to a novel silicified cancer cell immunotherapy in a mouse model of disseminated serous epithelial ovarian cancer.