Vaccination generates functional progenitor tumor-specific CD8 T cells and long-term tumor control.

Background: Immune checkpoint blockade (ICB) therapies are an important treatment for patients with advanced cancers; however, only a subset of patients with certain types of cancer achieve durable remission. Cancer vaccines are an attractive strategy to boost patient immune responses, but less is known about whether and how immunization can induce long-term tumor immune reprogramming and arrest cancer progression. We developed a clinically relevant genetic cancer mouse model in which hepatocytes sporadically undergo oncogenic transformation.

Vaccination generates functional progenitor tumor-specific CD8 T cells and long-term tumor control.

Background: Immune checkpoint blockade (ICB) therapies are an important treatment for patients with advanced cancers; however only a subset of patients with certain types of cancer achieves durable remissions. Cancer vaccines are an attractive strategy to boost patient immune responses, but less is known about whether and how immunization can induce long-term tumor immune reprogramming and arrest cancer progression. We developed a clinically-relevant genetic cancer mouse model in which hepatocytes sporadically undergo oncogenic transformation.

Tumor-Reactive CD8+ T Cells Enter a TCF1+PD-1- Dysfunctional State.

T cells recognize several types of antigens in tumors, including aberrantly expressed, nonmutated proteins, which are therefore shared with normal tissue and referred to as self/shared-antigens (SSA), and mutated proteins or oncogenic viral proteins, which are referred to as tumor-specific antigens (TSA). Immunotherapies such as immune checkpoint blockade (ICB) can activate T-cell responses against TSA, leading to tumor control, and also against SSA, causing immune-related adverse events (irAE). To improve anti-TSA immunity while limiting anti-SSA autoreactivity, we need to understand how tumor-specific CD8+ T cells (TST) and SSA-specific CD8+ T (SST) cells differentiate in response to cognate antigens during tumorigenesis.

Hallmarks of CD8 T cell dysfunction are established within hours of tumor antigen encounter before cell division.

Tumor-specific CD8+ T cells (TST) in patients with cancer are dysfunctional and unable to halt cancer progression. TST dysfunction, also known as exhaustion, is thought to be driven by chronic T cell antigen receptor (TCR) stimulation over days to weeks. However, we know little about the interplay between CD8 T cell function, cell division and epigenetic remodeling within hours of activation.

Precision delivery of liquid therapy into the arterial wall for the treatment of peripheral arterial disease.

Perfusion catheters have recently emerged as a novel approach to deliver liquid anti-proliferative agents into flow obstructed arterial segments. The purpose of this study was to determine the impact of luminal delivery pressure on liquid drug penetration into the vessel wall. An ex vivo model using harvested porcine carotid arteries and a two-dimensional computational model were utilized to determine the impact of delivery pressure of liquid therapy into the arterial wall.

Pre-Clinical Investigation of Keratose as an Excipient of Drug Coated Balloons.

Background: Drug-coated balloons (DCBs), which deliver anti-proliferative drugs with the aid of excipients, have emerged as a new endovascular therapy for the treatment of peripheral arterial disease. In this study, we evaluated the use of keratose (KOS) as a novel DCB-coating excipient to deliver and retain paclitaxel.

Methods: A custom coating method was developed to deposit KOS and paclitaxel on uncoated angioplasty balloons.

Delivery of Cell-Specific Aptamers to the Arterial Wall with an Occlusion Perfusion Catheter.

Current strategies to prevent restenosis following endovascular treatment include the local delivery of anti-proliferative agents to inhibit vascular smooth muscle cell (VSMC) proliferation and migration. These agents, not specific to VSMCs, are deposited on the luminal surface and therefore target endothelial cells and delay vascular healing. Cell-targeted therapies, (e.

and Assessment of Keratose as a Novel Excipient of Paclitaxel Coated Balloons.

Drug coated balloons (DCB) are continually improving due to advances in coating techniques and more effective excipients. Paclitaxel, the current drug choice of DCB, is a microtubule-stabilizing chemotherapeutic agent that inhibits smooth muscle cell proliferation. Excipients work to promote coating stability and facilitate paclitaxel transfer and retention at the target lesion, although current excipients lack sustained, long-term paclitaxel retention.

Coating and Pharmacokinetic Evaluation of Air Spray Coated Drug Coated Balloons.

Drug coated balloons (DCB) are becoming the standard-care treatment for peripheral arterial disease (PAD). DCB use excipients to transfer and retain anti-proliferative drugs, such as paclitaxel. Excipients thus play a vital role in the design and function of DCB, however methods to coat balloons with excipients and anti-proliferative drugs remain unknown.