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.
BioElectroMed Corp., Burlingame, CA, USA. rich@bioelectromed.com
Richard
R
Nuccitelli
Kevin
K
Tran
Kaying
K
Lui
Joanne
J
Huynh
Brian
B
Athos
Mark
M
Kreis
Pamela
P
Nuccitelli
Edward C
EC
De Fabo
D055011:Ablation Techniques / Q000379:methods*; D000818:Animals; D017209:Apoptosis / Q000528:radiation effects; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D004599:Electric Stimulation Therapy / Q000379:methods*; D007109:Immunity / Q000276:immunology*; D020287:In Situ Nick-End Labeling; D008545:Melanoma / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D008546:Melanoma, Experimental / Q000276:immunology / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D051379:Mice; D008810:Mice, Inbred C57BL; D050997:Nanomedicine / Q000379:methods*; D015203:Reproducibility of Results; D012878:Skin Neoplasms / Q000276:immunology / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D012880:Skin Pigmentation / Q000528:radiation effects; D013696:Temperature; D014466:Ultraviolet Rays