Modulating the Cell Death Immune Response for Electroporation Treatments.

Irreversible electroporation (IRE) is a minimally invasive ablation technique that compromises integrity of the cell membrane through the application of short duration, high voltage electric pulses to induce cell death. Adverse effects of IRE such as muscle contractions are reduced with higher frequency biphasic pulsing, commonly known as high-frequency irreversible electroporation (H-FIRE). IRE and H-FIRE treatments have shown to increase immune activation through the induction of both immediate and delayed cell death, indicated by the release of damage-associated molecular pathways, antigens, and proteins.

Irreversible electroporation promotes a pro-inflammatory tumor microenvironment and anti-tumor immunity in a mouse pancreatic cancer model.

Pancreatic cancer is a significant cause of cancer-related mortality and often presents with limited treatment options. Pancreatic tumors are also notorious for their immunosuppressive microenvironment. Irreversible electroporation (IRE) is a non-thermal tumor ablation modality that employs high-voltage microsecond pulses to transiently permeabilize cell membranes, ultimately inducing cell death.

Harnessing the Electrochemical Effects of Electroporation-Based Therapies to Enhance Anti-tumor Immune Responses.

This study introduces a new method of targeting acidosis (low pH) within the tumor microenvironment (TME) through the use of cathodic electrochemical reactions (CER). Low pH is oncogenic by supporting immunosuppression. Electrochemical reactions create local pH effects when a current passes through an electrolytic substrate such as biological tissue.

High-frequency irreversible electroporation improves survival and immune cell infiltration in rodents with malignant gliomas.

Background: Irreversible electroporation (IRE) has been previously investigated in preclinical trials as a treatment for intracranial malignancies. Here, we investigate next generation high-frequency irreversible electroporation (H-FIRE), as both a monotherapy and a combinatorial therapy, for the treatment of malignant gliomas.

Methods: Hydrogel tissue scaffolds and numerical modeling were used to inform H-FIRE pulsing parameters for our orthotopic tumor-bearing glioma model.

Exploration of Novel Pathways Underlying Irreversible Electroporation Induced Anti-Tumor Immunity in Pancreatic Cancer.

Advancements in medical sciences and technologies have significantly improved the survival of many cancers; however, pancreatic cancer remains a deadly diagnosis. This malignancy is often diagnosed late in the disease when metastases have already occurred. Additionally, the location of the pancreas near vital organs limits surgical candidacy, the tumor's immunosuppressive environment limits immunotherapy success, and it is highly resistant to radiation and chemotherapy.

Generation of Tumor-activated T cells Using Electroporation.

Expansion of cytotoxic T lymphocytes (CTLs) is a crucial step in almost all cancer immunotherapeutic methods. Current techniques for expansion of tumor-reactive CTLs present major limitations. This study introduces a novel method to effectively produce and expand tumor-activated CTLs using high-voltage pulsed electric fields.

Separation of Macrophages and Fibroblasts Using Contactless Dielectrophoresis and a Novel ImageJ Macro.

This study presents a label-free method of separating macrophages and fibroblasts, cell types critically associated with tumors. Contactless dielectrophoresis (DEP) devices were used to separate fibroblasts from macrophages by selectively trapping one population. An ImageJ macro was developed to determine the percentage of each population moving or stationary at a given point in time in a video.

Electrospun acellular scaffolds for mimicking the natural anisotropy of the extracellular matrix.

In tissue engineering, the use of scaffolds helps establish a synergistic relationship between the scaffolds and the tissues by improving cell-scaffold interaction. This interaction is enhanced when physiologically relevant biophysical cues are replicated in the artificial scaffolds. Here, we present a novel scaffold that mimics the natural anisotropy of the native extracellular matrix of tissues, fabricated by electrospinning a combination of three polymers: polycaprolactone (PCL), polyvinylidene fluoride (PVDF) and polyaniline (PANI).

Understanding the role of calcium-mediated cell death in high-frequency irreversible electroporation.

High-frequency irreversible electroporation (H-FIRE) is an emerging electroporation-based therapy used to ablate cancerous tissue. Treatment consists of delivering short, bipolar pulses (1-10μs) in a series of 80-100 bursts (1 burst/s, 100μs on-time). Reducing pulse duration leads to reduced treatment volumes compared to traditional IRE, therefore larger voltages must be applied to generate ablations comparable in size.

The feasibility of using dielectrophoresis for isolation of glioblastoma subpopulations with increased stemness.

Cancer stem cells (CSCs) are aggressive subpopulations with increased stem-like properties. CSCs are usually resistant to most standard therapies and are responsible for tumor repropagation. Similar to normal stem cells, isolation of CSCs is challenging due to the lack of reliable markers.