Non‐thermal Nanoelectroablation of UV‐induced Murine Melanomas Stimulates an Immune Response

Non‐thermal nanoelectroablation therapy completely ablates UV‐induced murine melanomas. C57/BL6‐HGF/SF transgenic mice were exposed to UV radiation as pups and began to develop visible melanomas 5–6 months later. We have treated 27 of these melanomas in 14 mice with nanosecond pulsed electric field (nsPEF) therapy delivering 2000 electric pulses each 100 ns long and 30 kV/cm at a rate of 5–7 pulses per second. All nanoelectroablated melanoma tumors began to shrink within a day after treatment and gradually disappeared over a period of 12–29 days. Pyknosis of nuclei was evident within 1 h of nsPEF treatment, and DNA fragmentation as detected by TUNEL staining was evident by 6 h after nsPEF treatment. In a melanoma allograft system, nsPEF treatment was superior to tumor excision at accelerating secondary tumor rejection in immune‐competent mice, suggesting enhanced stimulation of a protective immune response by nsPEF‐treated melanomas. This is supported by the presence of CD4+‐T cells within treated tumors as well as within untreated tumors located in mice with other melanomas that had been treated with nanoelectroablation at least 19 days earlier.

[1]  M. Tucker,et al.  Rising Melanoma Incidence Rates of the Trunk among Younger Women in the United States , 2010, Cancer Epidemiology, Biomarkers & Prevention.

[2]  P. Thomas Vernier,et al.  DNA Electrophoretic Migration Patterns Change after Exposure of Jurkat Cells to a Single Intense Nanosecond Electric Pulse , 2011, PloS one.

[3]  Juergen F Kolb,et al.  Selective field effects on intracellular vacuoles and vesicle membranes with nanosecond electric pulses. , 2005, Biophysical journal.

[4]  Karl H. Schoenbach,et al.  Nanosecond pulsed electric fields induce apoptosis in p53-wildtype and p53-null HCT116 colon carcinoma cells , 2007, Apoptosis.

[5]  Juergen F. Kolb,et al.  Nanosecond pulsed electric fields cause melanomas to self-destruct , 2006 .

[6]  K. Schoenbach.  Chapter 2. Bioelectric Effect of Intense Nanosecond Pulses , 2014 .

[7]  F. Andre,et al.  Gadolinium blocks membrane permeabilization induced by nanosecond electric pulses and reduces cell death. , 2010, Bioelectrochemistry.

[8]  Ravindra P. Joshi,et al.  Ultrashort electrical pulses open a new gateway into biological cells , 2004 .

[9]  Richard Nuccitelli,et al.  Optimized nanosecond pulsed electric field therapy can cause murine malignant melanomas to self‐destruct with a single treatment , 2010, International journal of cancer.

[10]  P. Thomas Vernier,et al.  Life Cycle of an Electropore: Field-Dependent and Field-Independent Steps in Pore Creation and Annihilation , 2010, The Journal of Membrane Biology.

[11]  K. Schoenbach,et al.  Long Term Survival of Mice with Hepatocellular Carcinoma after Pulse Power Ablation with Nanosecond Pulsed Electric Fields , 2012, Technology in cancer research & treatment.

[12]  Zap [extreme voltage for fighting diseases] , 2006 .

[13]  Richard L Gregory,et al.  Zap! , 1991, IEEE Spectrum.

[14]  Stephen J. Beebe,et al.  An apoptosis targeted stimulus with nanosecond pulsed electric fields (nsPEFs) in E4 squamous cell carcinoma , 2011, Apoptosis.

[15]  K. Schoenbach,et al.  Nanosecond pulsed electric field (nsPEF) effects on cells and tissues: apoptosis induction and tumor growth inhibition , 2001, PPPS-2001 Pulsed Power Plasma Science 2001. 28th IEEE International Conference on Plasma Science and 13th IEEE International Pulsed Power Conference. Digest of Papers (Cat. No.01CH37251).

[16]  Dmitri V. Krysko,et al.  Clearance of apoptotic and necrotic cells and its immunological consequences , 2006, Apoptosis.

[17]  K. H. Schoenbach,et al.  Effects of submicrosecond, high intensity pulsed electric fields on living cells - intracellular electromanipulation , 2003 .

[18]  Juergen F Kolb,et al.  Leukemic cell intracellular responses to nanosecond electric fields. , 2004, Biochemical and biophysical research communications.

[19]  K. Schoenbach,et al.  Nanosecond pulsed electric fields stimulate apoptosis without release of pro-apoptotic factors from mitochondria in B16f10 melanoma. , 2010, Archives of biochemistry and biophysics.

[20]  Glenn Merlino,et al.  Ultraviolet B but not Ultraviolet A Radiation Initiates Melanoma , 2004, Cancer Research.

[21]  Bennett L Ibey,et al.  Lipid nanopores can form a stable, ion channel-like conduction pathway in cell membrane. , 2009, Biochemical and biophysical research communications.

[22]  Juergen F. Kolb,et al.  A new pulsed electric field therapy for melanoma disrupts the tumor's blood supply and causes complete remission without recurrence , 2009, International journal of cancer.

[23]  Juergen F Kolb,et al.  Long‐lasting plasma membrane permeabilization in mammalian cells by nanosecond pulsed electric field (nsPEF) , 2007, Bioelectromagnetics.

[24]  Sean Davis,et al.  Interferon-γ links ultraviolet radiation to melanomagenesis in mice. , 2011, Nature.

[25]  Laura Marcu,et al.  Nanoelectropulse-induced phosphatidylserine translocation. , 2004, Biophysical journal.

[26]  A. Sober,et al.  An estimate of the annual direct cost of treating cutaneous melanoma. , 1998, Journal of the American Academy of Dermatology.

[27]  K. Schoenbach,et al.  Apoptosis initiation and angiogenesis inhibition: melanoma targets for nanosecond pulsed electric fields , 2010, Pigment cell & melanoma research.

[28]  K. Schoenbach,et al.  Nanosecond, high‐intensity pulsed electric fields induce apoptosis in human cells , 2003, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[29]  M. Manns,et al.  Apoptotic, but not necrotic, tumor cell vaccines induce a potent immune response in vivo , 2003, International journal of cancer.

[30]  P. Duray,et al.  Neonatal sunburn and melanoma in mice , 2001, Nature.

[31]  Laura Marcu,et al.  In vitro and in vivo evaluation and a case report of intense nanosecond pulsed electric field as a local therapy for human malignancies , 2007, International journal of cancer.