Stephen J Beebe*

Frank Reidy Research Center for Bioelectrics, Old Dominion University, Virginia, USA

*Corresponding Author: Stephen J Beebe, Frank Reidy Research Center for Bioelectrics, Old Dominion University, Virginia, USA.

Received: May 06, 2021; Published: July 08, 2021

Abstract

  Nanopulse stimulation (NPS) presents a novel approach for cancer treatment. It applies high electric field pulses with ultrashort durations and fast rise-fall times, affecting the plasma membrane and intracellular structures and functions, inducing regulated cell death mechanisms that are immunogenic, eliminating tumors and their immunosuppressive tumor microenvironment, and activating innate and adaptive immune mechanisms. This results in tumor ablation and in situ vaccination against rat liver and mouse breast cancer. Here I provide a general overview of this technology and some finer points of the pulsed power technology.

Keywords: Pulsed Power; Tumor Ablation; In Situ Vaccination; Immunosuppression; Innate Immunity; Adaptive Immunity

References

1. Beebe SJ. “Preclinical Studies on Nanosecond Pulses”. In Handbook of Electroporation, Miklavčič D., Ed.; Springer, Cham (2016): 1543-1562
2. Beebe SJ. “Regulated and Apoptotic Cell Death After Nanosecond Electroporation”. In Handbook of Electroporation. Miklavčič D., Ed.; Springer, Cham. (2016): 511-528.
3. Beebe SJ. “Regulated Cell Death (RCD) by Caspase-Dependent Mechanisms”. In Bioelectrics, Akiyama H., Heller R, Eds.; Springer Japan (2016): 238-254.
4. Schoenbach KH., et al. “The effect of pulsed electric fields on biological cells: Experiments and applications”. IEEE Trans on Plasma Science 25 (1997): 284-292.
5. Schoenbach KH., et al. “Intracellular effect of ultrashort electrical pulses”. Bioelectromagnetics 22 (2001): 440-448.
6. Schoenbac K H., et al. “Ultrashort electrical pulses open a new gateway into biological cells”. IEEE 92 (2004): 1122-1137.
7. Cole KS. “Electric impedance of marine egg membranes”. Transactions of the Faraday Society 23 (1937): 966-972.
8. Schwan HP. “Dielectric properties of the cell surface and electric field effects on cells”. Studia Biophysica 110 (1985): 13-18.
9. Semenov I., et al. “Recruitment of the intracellular Ca2+ by ultrashort electric stimuli: the impact of pulse duration”. Cell Calcium 54 (2013): 145-150.
10. Beebe SJ., et al. “Transient features in nanosecond pulsed electric fields differentially modulate mitochondria and viability”. PLoS One 7 (2012): e51349.
11. Beebe SJ., et al. “Induction of Cell Death Mechanisms and Apoptosis by Nanosecond Pulsed Electric Fields (nsPEFs)”. Cells 2 (2013): 136-162.
12. Beebe SJ. “Considering effects of nanosecond pulsed electric fields on proteins”. Bioelectrochemistry 103 (2015): 52-59.
13. Keep O., et al. “Immunogenic cell death modalities and their impact on cancer treatment”. Apoptosis 14 (2009): 364-375.
14. Galluzzi L., et al. “Consensus guidelines for the definition, detection, and interpretation of immunogenic cell death”. Journal of Immunotherapy Cancer 8 (2020): e000337.
15. Guo S., et al. “Nano-pulse stimulation induces potent immune responses, eradicating local breast cancer while reducing distant metastases”. International Journal of Cancer 142 (2018): 629-640.
16. Nuccitelli R., et al. “Nano-Pulse Stimulation is a physical modality that can trigger immunogenic tumor cell death”. Journal of Immunotherapy Cancer 5 (2017): 32.
17. Vogelstein B., et al. “Cancer genome landscapes”. Science 339 (2013): 1546-1558.
18. Horne SD., et al. “Stress, genomic adaptation, and the evolutionary trade-off”. Frontiers in Genetics 5 (2014): 92.
19. Salk JJ., et al. “Mutational heterogeneity in human cancers: origin and consequences”. Annual Review of Pathology 5 (2010): 51-75.
20. Zhao B., et al. “Intratumor heterogeneity alters most effective drugs in designed combinations”. Proceedings of the National Academy of Sciences of the United States of America 111 (2014): 10773-10778.
21. Dean M., et al. “Tumour stem cells and drug resistance”. Nature Reviews Cancer 5 (2005): 275-284.
22. Beck B and Blanpain C. “Unravelling cancer stem cell potential”. Nature Reviews Cancer 13 (2013): 727-738.
23. Easwaran H., et al. “Cancer epigenetics: tumor heterogeneity, plasticity of stem-like states, and drug resistance”. Molecular Cell 54 (2014): 716-727.
24. Bird A. “Perceptions of epigenetics”. Nature 447 (2007): 396-398.
25. Waddington CH. “The epigenotype”. International Journal of Epidemiology 41 (2012): 10-13.
26. Byler S., et al. “Genetic and epigenetic aspects of breast cancer progression and therapy”. Anticancer Research 34 (2014): 1071-1077.
27. Nowell PC. “The clonal evolution of tumor cell populations”. Science 194 (1976): 23-28.
28. Heng HH. “The genome-centric concept: resynthesis of evolutionary theory”. Bioessays 31 (2009): 512-525.
29. Heng HH., et al. “The evolutionary mechanism of cancer”. Journal of Cellular Biochemistry 109 (2010): 1072-1084.
30. Horne SD., et al. “Stress, genomic adaptation, and the evolutionary trade-off”. Frontiers in Genetics 5 (2014): 92.
31. McGranahan N and Swanton C. “Biological and therapeutic impact of intratumor heterogeneity in cancer evolution”. Cancer Cell 27 (2015): 15-26.
32. Heng HH., et al. “Cancer progression by non-clonal chromosome aberrations”. Journal of Cellular Biochemistry 98 (2006): 1424-1435.
33. Heng HH. “The genome-centric concept: resynthesis of evolutionary theory”. Bioessays 31 (2009): 512-525.
34. Hanahan D and Weinberg RA. “The hallmarks of cancer”. Cell 100 (2000): 57-70.
35. Hanahan D and Weinberg RA. “Hallmarks of cancer: the next generation”. Cell 144 (2011): 646-674.
36. Al-Lazikani B., et al. “Combinatorial drug therapy for cancer in the post-genomic era”. Nature Biotechnology 30 (2012): 679-692.
37. Gatzka MV. “Targeted tumor therapy remixed-an update on the use of small-molecule drugs in combination therapies”. Cancers (Basel) 10 (2018): 155.
38. Chen R., et al. “A protective effect after clearance of orthotopic rat hepatocellular carcinoma by nanosecond pulsed electric fields”. European Journal of Cancer 50 (2014): 2705-2713.
39. Lassiter BP., et al. “Nano-Pulse Stimulation Ablates Orthotopic Rat Hepatocellular Carcinoma and Induces Innate and Adaptive Memory Immune Mechanisms that Prevent Recurrence”. Cancers (Basel) 10 (2018): 69.
40. Beebe SJ., et al. “Nanopulse stimulation (NPS) induces tumor ablation and immunity in orthotopic 4T1 mouse breast cancer: A review”. Cancers (Basel) 10 (2018): 97.
41. Chen X., et al. “Apoptosis initiation and angiogenesis inhibition: melanoma targets for nanosecond pulsed electric fields”. Pigment Cell and Melanoma Research 23 (2010): 554-563.
42. Chen X., et al. “Long term survival of mice with hepatocellular carcinoma after pulse power ablation with nanosecond pulsed electric fields”. Technology in Cancer Research and Treatment 11 (2012): 83-93.
43. Beebe SJ. “Ultrashort pulse induced regulated cell death”. In Ultrashort Electric Pulse Effects in Biology and Medicine. Beebe, S. J, Joshi, R, Schoenbach, K.H, Xiao, S.; Springer Singapore (2021): 227-263.
44. Uhl M., et al. “Autophagy within the antigen donor cell facilitates efficient antigen cross-priming of virus-specific CD8+ T cells”. Cell Death and Differentiation 16 (2009): 991-1005.
45. Kroemer G., et al. “Immunogenic cell death in cancer therapy”. Annual Review on Immunology 31 (2013): 51-72.
46. Galluzzi L., et al. “Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018”. Cell Death and Differentiation 25 (2018): 486-541.
47. Guo ZS., et al. “Oncolytic immunotherapy: Dying the right way is a key to eliciting potent antitumor immunity”. Frontiers in Oncology 4 (2014): 74.
48. Yatim N., et al. “RIPK1 and NF-κB signaling in dying cells determines cross-priming of CD8⁺ T cells”. Science 350 (2015): 328-333.
49. Kepp O., et al. “Consensus guidelines for the detection of immunogenic cell death”. Oncoimmunology 3 (2014): e955691.
50. Inoue H and Tani K. “Multimodal immunogenic cancer cell death as a consequence of anticancer cytotoxic treatments”. Cell Death and Differentiation 21 (2014): 39-49.
51. Guo S., et al. “Nano-pulse stimulation for the treatment of pancreatic cancer and the changes in immune profile”. Cancers (Basel) 10 (2018): 217.
52. Rossi A., et al. “Mechanisms and immunogenicity of nsPEF-induced cell death in B16F10 melanoma tumors”. Scientific Report 9 (2019): 431.

Citation

Citation: Stephen J Beebe. “Nanopulse Stimulation as a Possible Immunotherapy”.Acta Scientific Medical Sciences 5.8 (2021): 10-14.

Copyright

Copyright: © 2021 Stephen J Beebe. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.