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July 23-25, 2018 | Moscow, Russia

12

th

World Cancer Congress

Journal of Medical Oncology and Therapeutics | Volume: 3

N

ano-Pulse Stimulation (NPS) is a technology based on

pulsed power physics, used for decades in high-powered

physics and military applications. Electrical energy is stored and

released in nanosecond bursts, producing instantaneous high

power and low, non-thermal energy. Since biological cells have

not experienced NPS in evolutionary history, they can exhibit

unique intracellular responses. At NPS levels cells undergo

programmed cell death (PCD) and induce innate and adaptive

immune mechanisms while at low NPS levels cells can be

stimulated and activated. The transition of this technology from

physics scenarios to biologic and medical landscapes uniquely

combines expertise from engineers, physicists, biologists and

physicians.

Our NPS strategy uses 60-100 ns pulse durations and electric

fields up to 50 kV/cm. When orthotopic mouse mammary

and rat liver tumors are eliminated by NPS, animals are

protected by an immune-mediated, vaccine-like effect against

the same cancer. Immune responses are dynamic on several

therapeutic fronts. NPS directly eliminates primary tumors by

inducing regulated form(s) of immunogenic cell death. This is

accompanied by specific activation of natural killer cells and

NKT-cells expressing NKG2D and CD161 activation receptors.

In addition, dendritic cells (DCs), which are activated by dead

and dying cancer cells, induce cytotoxic T-cells expressing

adaptive memory phenotypes. Importantly, NPS eliminates

immunosuppressive cells in the tumor microenvironment and

blood. In the mouse model, a strong abscopal effect occurs

including reduction of spontaneous distant metastases and

eradication of second untreated lesions.

Non-lethal NPS can activate DCs. NPS attenuates respiration

in DCs and other cells by affecting electron transport

chain complexes I and IV increasing superoxide anions in

mitochondria, which activate DCs that express activation

markers and cytokine secretion. Higher NPS induces opening

of the permeability transition pore and induces PCD. How

these and other intracellular NPS-induced mechanisms lead to

ablation-induced immune responses is under investigation.

Speaker Biography

Stephen J Beebe is a Research Professor in the Frank Reidy Research Center for

Bioelectrics at Old Dominion University (ODU). He received his PhD in Medical Sciences

(Pharmacology) at the University of Toledo College of Medicine in 1982 and was a post-

doctoral fellow at the Howard Hughes Medical Institute, Department of Molecular

Physiology and Biophysics, Vanderbilt University School of Medicine. He was a Fulbright

andMarshallScholar inOslo

,Norway.He

istheauthorof125peerreviewedmanuscripts

and books chapters. He was awarded two NIH grants analyzing structure and function

of Protein Kinase A and cAMP signal transduction. He now investigates mechanisms of

NanoPulse Stimulation (NPS) in cancer and biology. He has trained over 30 graduate

students and post-doctoral fellows, is a member of Editorial Boards for four journals

and is the Chair of the ODU Institutional Animal Care and Use Committee (IACUC).

e:

sbeebe@odu.edu

Stephen J Beebe

1

Brittany Lassiter

2

Siqi Guo

3

Old Dominion University, USA

Translational research with nanosecond pulse stimulation for Immuno-Oncology

applications