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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.Heistheauthorof125peerreviewedmanuscripts
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
1
Brittany Lassiter
2
Siqi Guo
3
Old Dominion University, USA
Translational research with nanosecond pulse stimulation for Immuno-Oncology
applications