Tumor Targeting by Peptide-Decorated Gold Nanoparticles.

Cancer remains one of the most important challenges in biomedical sciences. Chemotherapeutic agents are very potent molecules that exhibit a significant level of toxicity in numerous tissues of the body, particularly in those characterized by high proliferative activity, such as the bone marrow. The scenario is even more complex in the case of the central nervous system, and in particular brain tumors, where the blood brain barrier limits the efficacy of drug therapies.

Histamine and T helper cytokine-driven epithelial barrier dysfunction in allergic rhinitis.

Background: Allergic rhinitis (AR) is characterized by mucosal inflammation, driven by activated immune cells. Mast cells and T2 cells might decrease epithelial barrier integrity in AR, maintaining a leaky epithelial barrier.

Objective: We sought to investigate the role of histamine and T2 cells in driving epithelial barrier dysfunction in AR.

Immunotherapy with subcutaneous immunogenic autologous tumor lysate increases murine glioblastoma survival.

Immunotherapeutic strategies for glioblastoma, the most frequent malignant primary brain tumor, aim to improve its disastrous consequences. On top of the standard treatment, one strategy uses T cell activation by autologous dendritic cells (DC) ex vivo loaded with tumor lysate to attack remaining cancer cells. Wondering whether 'targeting' in vivo DCs could replace these ex vivo ones, immunogenic autologous tumor lysate was used to treat glioma-inoculated mice in the absence of ex vivo loaded DCs.

Dynamic stroma reorganization drives blood vessel dysmorphia during glioma growth.

Glioma growth and progression are characterized by abundant development of blood vessels that are highly aberrant and poorly functional, with detrimental consequences for drug delivery efficacy. The mechanisms driving this vessel dysmorphia during tumor progression are poorly understood. Using longitudinal intravital imaging in a mouse glioma model, we identify that dynamic sprouting and functional morphogenesis of a highly branched vessel network characterize the initial tumor growth, dramatically changing to vessel expansion, leakage, and loss of branching complexity in the later stages.

Preclinical efficacy of immune-checkpoint monotherapy does not recapitulate corresponding biomarkers-based clinical predictions in glioblastoma.

Glioblastoma (GBM) is resistant to most multimodal therapies. Clinical success of immune-checkpoint inhibitors (ICIs) has spurred interest in applying ICIs targeting CTLA4, PD1 or IDO1 against GBM. This amplifies the need to ascertain GBM's intrinsic susceptibility (or resistance) toward these ICIs, through clinical biomarkers that may also "guide and prioritize" preclinical testing.

Pathogen response-like recruitment and activation of neutrophils by sterile immunogenic dying cells drives neutrophil-mediated residual cell killing.

Innate immune sensing of dying cells is modulated by several signals. Inflammatory chemokines-guided early recruitment, and pathogen-associated molecular patterns-triggered activation, of major anti-pathogenic innate immune cells like neutrophils distinguishes pathogen-infected stressed/dying cells from sterile dying cells. However, whether certain sterile dying cells stimulate innate immunity by partially mimicking pathogen response-like recruitment/activation of neutrophils remains poorly understood.

Clinical-Grade Human Multipotent Adult Progenitor Cells Block CD8+ Cytotoxic T Lymphocytes.

Unlabelled: : MultiStem cells are clinical-grade multipotent adult bone marrow-derived progenitor cells (MAPCs), with extensive replication potential and broader differentiation capacity compared with mesenchymal stem cells. Human MAPCs suppress T-cell proliferation induced by alloantigens and mutually interact with allogeneic natural killer cells. In this study, the interaction between MultiStem and CD8 cytotoxic T lymphocytes (CTLs) was addressed for the first time.

Development of siRNA-loaded chitosan nanoparticles targeting Galectin-1 for the treatment of glioblastoma multiforme via intranasal administration.

Galectin-1 (Gal-1) is a naturally occurring galactose-binding lectin, which is overexpressed in glioblastoma multiforme (GBM). Gal-1 is associated with tumor progression, and is a potent immune suppressor in the tumor micro-environment. To inhibit Gal-1 in GBM, an effective therapy is required that reaches the central nervous system tumor, with limited systemic effects.

Development and evaluation of well-tolerated and tumor-penetrating polymeric micelle-based dry powders for inhaled anti-cancer chemotherapy.

Despite the direct access to the lung offered by the inhalation route, drug penetration into lung tumors could remain an important issue. In this study, folate-polyethylene glycol-hydrophobically-modified dextran (F-PEG-HMD) micelles were developed as an effective pulmonary drug delivery system to reach and penetrate lung tumors and cancer cells. The F-PEG-HMD micelles were able to enter HeLa and M109-HiFR, two folate receptor-expressing cancer cell lines, in vitro, and in vivo after administration by inhalation to orthotopic M109-HiFR lung tumor grafted mice.

Exploiting the Immunogenic Potential of Cancer Cells for Improved Dendritic Cell Vaccines.

Cancer immunotherapy is currently the hottest topic in the oncology field, owing predominantly to the discovery of immune checkpoint blockers. These promising antibodies and their attractive combinatorial features have initiated the revival of other effective immunotherapies, such as dendritic cell (DC) vaccinations. Although DC-based immunotherapy can induce objective clinical and immunological responses in several tumor types, the immunogenic potential of this monotherapy is still considered suboptimal.

Formulations for Intranasal Delivery of Pharmacological Agents to Combat Brain Disease: A New Opportunity to Tackle GBM?

Despite recent advances in tumor imaging and chemoradiotherapy, the median overall survival of patients diagnosed with glioblastoma multiforme does not exceed 15 months. Infiltration of glioma cells into the brain parenchyma, and the blood-brain barrier are important hurdles to further increase the efficacy of classic therapeutic tools. Local administration methods of therapeutic agents, such as convection enhanced delivery and intracerebral injections, are often associated with adverse events.

Altered galectin-1 serum levels in patients diagnosed with high-grade glioma.

High-grade gliomas (HGG) are the most common and most aggressive intrinsic human brain tumors in adults. Galectin-1, a glycan-binding protein that is overexpressed in HGG, has been shown to contribute significantly to the aggressive nature of HGG. It is unknown whether increased galectin-1 expression levels are exclusively found at the tumor site or whether galectin-1 can also be detected in the serum of HGG patients.