Integrating IL-12 mRNA nanotechnology with SBRT eliminates T cell exhaustion in preclinical models of pancreatic cancer.

Pronounced T cell exhaustion characterizes immunosuppressive tumors, with the tumor microenvironment (TME) employing multiple mechanisms to elicit this suppression. Traditional immunotherapies, such as immune checkpoint blockade, often fail due to their focus primarily on T cells. To overcome this, we utilized a proinflammatory cytokine, interleukin (IL)-12, that re-wires the immunosuppressive TME by inducing T cell effector function while also repolarizing immunosuppressive myeloid cells.

Interlaboratory comparison of endotoxin contamination assessment of nanomaterials.

Endotoxin contamination is a significant hurdle to the translation of nanomaterials for biomedical applications. Multiple reports now describe that more than one-third of nanomaterials fail early pre-clinical assessment due to levels of endotoxin above regulatory requirements. Additionally, most immunological studies or studies testing nanomaterials in the literature lack inclusion of this assessment, which may lead to false-positive or false-negative results if high levels of the contaminant are present.

Inflammation related to inhalation of nano and micron sized iron oxides: a systematic review.

Inhalation exposure to iron oxide occurs in many workplaces and respirable aerosols occur during thermal processes (e.g. welding, casting) or during abrasion of iron and steel products (e.

Biodistribution and histological analysis of iron oxide-dextran nanoparticles in wistar rats.

Iron oxide nanoparticles (IONP) are showing promise in many biomedical applications. One of these- magnetic hyperthermia- utilizes externally applied alternating magnetic fields and tumor-residing magnetic nanoparticles to generate localized therapeutic temperature elevations. Magnetic hyperthermia is approved in Europe to treat glioblastoma and is undergoing clinical assessment in the United States to treat prostate cancer.

Local Delivery of SBRT and IL12 by mRNA Technology Overcomes Immunosuppressive Barriers to Eliminate Pancreatic Cancer.

Unlabelled: The immunosuppressive milieu in pancreatic cancer (PC) is a significant hurdle to treatments, resulting in survival statistics that have barely changed in 5 decades. Here we present a combination treatment consisting of stereotactic body radiation therapy (SBRT) and IL-12 mRNA lipid nanoparticles delivered directly to pancreatic murine tumors. This treatment was effective against primary and metastatic models, achieving cures in both settings.

New insights into the responder/nonresponder divide in rectal cancer: Damage-induced Type I IFNs dictate treatment efficacy and can be targeted to enhance radiotherapy.

Rectal cancer ranks as the second leading cause of cancer-related deaths. Neoadjuvant therapy for rectal cancer patients often results in individuals that respond well to therapy and those that respond poorly, requiring life-altering excision surgery. It is inadequately understood what dictates this responder/nonresponder divide.

Testing the Effects of Magnetic Hyperthermia in 2D Cell Culture.

Magnetic hyperthermia is an innovative thermal therapy for the treatment of solid malignancies. This treatment approach utilizes magnetic nanoparticles that are stimulated by alternating magnetic fields to induce temperature elevations in tumor tissue, resulting in cell death. Magnetic hyperthermia is clinically approved for treating glioblastoma in Europe and is undergoing clinical evaluation for prostate cancer in the United States.

CD73 and PD-L1 dual blockade amplifies antitumor efficacy of SBRT in murine PDAC models.

Background: Stereotactic body radiotherapy (SBRT) induces immunogenic cell death, leading to subsequent antitumor immune response that is in part counterbalanced by activation of immune evasive processes, for example, upregulation of programmed cell death-ligand 1 (PD-L1) and adenosine generating enzyme, CD73. CD73 is upregulated in pancreatic ductal adenocarcinoma (PDAC) compared with normal pancreatic tissue and high expression of CD73 in PDACs is associated with increased tumor size, advanced stage, lymph node involvement, metastasis, PD-L1 expression and poor prognosis. Therefore, we hypothesized that blockade of both CD73 and PD-L1 in combination with SBRT might improve antitumor efficacy in an orthotopic murine PDAC model.

Harnessing the Immunological Effects of Radiation to Improve Immunotherapies in Cancer.

Ionizing radiation (IR) is used to treat 50% of cancers. While the cytotoxic effects related to DNA damage with IR have been known since the early 20th century, the role of the immune system in the treatment response is still yet to be fully determined. IR can induce immunogenic cell death (ICD), which activates innate and adaptive immunity against the cancer.

Thermal ablation in pancreatic cancer: A scoping review of clinical studies.

Background: Pancreatic cancer is a deadly cancer with a 5-year survival rate less than 10%. Only 20% of patients are eligible to receive surgery at diagnosis. Hence, new therapies are needed to improve outcomes for non-surgical candidates.

Endotoxin contamination of engineered nanomaterials: Overcoming the hurdles associated with endotoxin testing.

Nanomaterials are highly susceptible to endotoxin contamination due their large surface-to-volume ratios and endotoxins propensity to associate readily to hydrophobic and cationic surfaces. Additionally, the stability of endotoxin ensures it cannot be removed efficiently through conventional sterilization techniques such as autoclaving and ionizing radiation. In recent times, the true significance of this hurdle has come to light with multiple reports from the United States Nanotechnology Characterization Laboratory, in particular, along with our own experiences of endotoxin testing from multiple Horizon 2020-funded projects which highlight the importance of this issue for the clinical translation of nanomaterials.

Comparing the Effects of Intracellular and Extracellular Magnetic Hyperthermia on the Viability of BxPC-3 Cells.

Magnetic hyperthermia involves the use of iron oxide nanoparticles to generate heat in tumours following stimulation with alternating magnetic fields. In recent times, this treatment has undergone numerous clinical trials in various solid malignancies and subsequently achieved clinical approval to treat glioblastoma and prostate cancer in 2011 and 2018, respectively. However, despite recent clinical advances, many questions remain with regard to the underlying mechanisms involved in this therapy.

Immunotoxicity Considerations for Next Generation Cancer Nanomedicines.

Although interest and funding in nanotechnology for oncological applications is thriving, translating these novel therapeutics through the earliest stages of preclinical assessment remains challenging. Upon intravenous administration, nanomaterials interact with constituents of the blood inducing a wide range of associated immunotoxic effects. The literature on the immunological interactions of nanomaterials is vast and complicated.