FDA Approval Summary: Nivolumab Plus Ipilimumab for the Treatment of Patients with Hepatocellular Carcinoma Previously Treated with Sorafenib.

On March 10, 2020, the U.S. Food and Drug Administration (FDA) granted accelerated approval to nivolumab in combination with ipilimumab for the treatment of patients with hepatocellular carcinoma (HCC) previously treated with sorafenib.

Benefit-Risk Summary of Nivolumab for the Treatment of Patients with Unresectable Advanced, Recurrent, or Metastatic Esophageal Squamous Cell Carcinoma After Prior Fluoropyrimidine- and Platinum-Based Chemotherapy.

On June 10, 2020, the U.S. Food and Drug Administration (FDA) approved nivolumab (OPDIVO; Bristol Myers Squibb, New York, NY) for the treatment of patients with unresectable advanced, recurrent, or metastatic esophageal squamous cell carcinoma (ESCC) after prior fluoropyrimidine- and platinum-based chemotherapy.

CD137 agonist-based combination immunotherapy enhances activated, effector memory T cells and prolongs survival in pancreatic adenocarcinoma.

Pancreatic ductal adenocarcinoma(PDAC) is resistant to the PD-1/PD-L1 blockade therapy. Previously, the combination of PD-1 blockade and vaccine therapy was shown to have a modest antitumor activity in murine models of PDAC. We used a murine syngeneic model of metastatic PDAC to identify, among multiple T cell modulators tested, which therapeutic agents in combination with the GVAX cancer vaccine and an anti-PD-1 antagonist antibody(αPD-1) are able to improve the survival.

Interrogating the immune-modulating roles of radiation therapy for a rational combination with immune-checkpoint inhibitors in treating pancreatic cancer.

Background: Radiation therapy (RT) has the potential to enhance the efficacy of immunotherapy, such as checkpoint inhibitors, which has dramatically altered the landscape of treatments for many cancers, but not yet for pancreatic ductal adenocarcinoma (PDAC). Our prior studies demonstrated that PD ligand-1 and indoleamine 2,3-dioxygenase 1 (IDO1) were induced on tumor epithelia of PDACs following neoadjuvant therapy including RT, suggesting RT may prime PDAC for PD-1 blockade antibody (αPD-1) or IDO1 inhibitor (IDO1i) treatments. In this study, we investigated the antitumor efficacy of the combination therapies with radiation and PD-1 blockade or IDO1 inhibition or both.

Adding combination immunotherapy consisting of cancer vaccine, anti-PD-1 and anti-CSF1R antibodies to gemcitabine improves anti-tumor efficacy in murine model of pancreatic ductal adenocarcinoma.

Background: Immunotherapy can take advantage of the immunogenic response that chemotherapy elicits in tumors. Gemcitabine is a standard agent used in the treatment of pancreatic cancer, with known effects on the tumor immune microenvironment. The combination immunotherapy of the GVAX cancer vaccine, anti-PD-1 antibody and anti-CSF-1R antibody has been shown to improve survival in a murine model of metastatic pancreatic adenocarcinoma.

Physical and chemical profiles of nanoparticles for lymphatic targeting.

Nanoparticles (NPs) have been gaining prominence as delivery vehicles for modulating immune responses to improve treatments against cancer and autoimmune diseases, enhancing tissue regeneration capacity, and potentiating vaccination efficacy. Various engineering approaches have been extensively explored to control the NP physical and chemical properties including particle size, shape, surface charge, hydrophobicity, rigidity and surface targeting ligands to modulate immune responses. This review examines a specific set of physical and chemical characteristics of NPs that enable efficient delivery targeted to secondary lymphoid tissues, specifically the lymph nodes and immune cells.

Particulate carrier systems as adjuvants for cancer vaccines.

To overcome the immunosuppressive milieu of malignancy and lack of well-defined antigens, potent adjuvants are needed for cancer immunotherapy. Numerous small molecular immunomodulators have the potential to fulfill this role. To enhance the immune response and decrease the toxicity, particulate systems including nanoparticles and macroparticles have been increasingly proposed as carriers for cancer antigen and adjuvant delivery.

Small molecule immunomodulation: the tumor microenvironment and overcoming immune escape.

Immunotherapy has led to a paradigm shift in the treatment of many advanced malignancies. Despite the success in treatment of tumors like non-small cell lung cancer (NSCLC) and melanoma, checkpoint inhibition-based immunotherapy has limitations. Many tumors, such as pancreatic cancer, are less responsive to checkpoint inhibitors, where patients tend to have a limited duration of benefit and where clinical responses are more robust in patients who are positive for predictive biomarkers.

Dissecting the Stromal Signaling and Regulation of Myeloid Cells and Memory Effector T Cells in Pancreatic Cancer.

Purpose: Myeloid cells are a prominent immunosuppressive component within the stroma of pancreatic ductal adenocarcinoma (PDAC). Previously, targeting myeloid cells has had limited success. Here, we sought to target the myeloid cells through modifying a specific stromal component.

Targeting myeloid-inflamed tumor with anti-CSF-1R antibody expands CD137+ effector T-cells in the murine model of pancreatic cancer.

Background: The pancreatic cancer vaccine, GVAX, induces novel lymphoid aggregates in the otherwise immune quiescent pancreatic ductal adenocarcinoma (PDAC). GVAX also upregulates the PD-1/PD-L1 pathway, and a pre-clinical model demonstrated the anti-tumor effects of combination GVAX and anti-PD-1 antibody therapy (GVAX/αPD-1). Resistance to GVAX was associated with an immune-suppressive myeloid cell infiltration, which may limit further therapeutic gains of GVAX/αPD-1 therapy.

Current Standards of Chemotherapy for Pancreatic Cancer.

Purpose: Pancreatic cancer has a dismal prognosis due to the early development of systemic metastatic disease. Chemotherapeutic agents are the only systemic therapy that offers patients meaningful benefit.

Methods: This study reviewed the literature for recently published Phase III clinical trials whose results have guided the current standards of chemotherapy for pancreatic cancer.

A Size-Selective Intracellular Delivery Platform.

Identifying and separating a subpopulation of cells from a heterogeneous mixture are essential elements of biological research. Current approaches require detailed knowledge of unique cell surface properties of the target cell population. A method is described that exploits size differences of cells to facilitate selective intracellular delivery using a high throughput microfluidic device.

Probing nanoparticle translocation across the permeable endothelium in experimental atherosclerosis.

Therapeutic and diagnostic nanomaterials are being intensely studied for several diseases, including cancer and atherosclerosis. However, the exact mechanism by which nanomedicines accumulate at targeted sites remains a topic of investigation, especially in the context of atherosclerotic disease. Models to accurately predict transvascular permeation of nanomedicines are needed to aid in design optimization.

Effect of computed tomography scanning parameters on gold nanoparticle and iodine contrast.

Purpose: Gold nanoparticles (gold-NPs) have lately been proposed as alternative contrast agents to iodine-based contrast agents (iodine-CA) for computed tomography (CT) angiography. The aims of this study were to confirm an appropriate environment in which to evaluate such novel contrast agents, to investigate the comparative contrast of iodine-CA versus gold-NP, and to determine optimal scanning parameters for gold-NP.

Materials And Methods: Three different clinical scanners were used to acquire CT images.