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Journal of Medical Oncology and Therapeutics | Volume 4
February 25-26, 2019 | Paris, France
13
th
World Cancer Congress
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 impacts like this
in evolutionary history, they can exhibit unique intracellular
responses that are noteworthy and remarkable. Under
high NPS conditions tumor cells undergo programmed cell
death (PCD) and innate and adaptive immune mechanisms
are activated. Under low NPS levels cells can be stimulated
and activated. The transition of this technology from physics
scenarios to biological and medical landscapes uniquely
combines expertise from engineers, physicists, biologists
and physicians.
NPS strategy for cancer treatment uses 60-100 ns pulse
durations and electric field strengths up to 50 kV/cm.
When orthotopic mouse mammary and rat hepatocellular
carcinoma tumors are eliminated by NPS, animals are
protected by an immune-mediated, vaccine-like effect
against exposure to 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 subsets of CD8+ natural killer cells and NKT-cells
expressing the 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, an abscopal effect occurs
including reduced spontaneous distant metastases and
eradication of second untreated lesions.
Non-lethal NPS can activate DCs. NPS attenuates respiration
in dendritic cells (DCs) and other cells by affecting complexes
I and IV in the electron transport chain (ETC) increasing levels
of superoxide anions in mitochondria, which presumably
activate DCs as indicated by expression of 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 are 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 was a Fulbright and Marshall
Scholar in Oslo, Norway. He is the author of 125 peer reviewed manuscripts 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.eduStephen J Beebe
Old Dominion University, USA
Translational research with Nanosecond Pulse Stimulation for Immuno-Oncology
applications