This dissertation includes a comprehensive current review of reversible electroporation
(EP) and other related physical gene transfection techniques; an overview of results of
electrochemogene therapy (ECGT) used to treat naturally occurring spontaneous neoplasms in
dogs; and the results of comprehensive, pre-clinical toxicology testing of electrogene therapy
(EGT) of a tumor-targeted version of interleukin-12 (IL-12) in mice.
Intralesional bleomycin (BLM) and feline interleukin-12 (fIL-12) DNA injection
combined with trans-lesional EP resulted in complete cure of two recurrent oral squamous cell
carcinomas and an acanthomatous ameloblastoma in a series of six cases of spontaneous
neoplasia in pet dogs. The three remaining dogs, which had no other treatment options, had
partial responses to ECGT. One of these dogs had mandibular melanoma with pulmonary and
lymph node metastases; one dog had cubital histiocytic sarcoma with spleen metastases; and one
had soft palate fibrosarcoma. Treatment of all six dogs was associated with minimal side effects,
was easy to perform, was associated with repair of bone lysis in cured dogs; improved the quality
of life for dogs with partial responses; and extended overall survival time.
For the purpose of meeting pre-clinical safety requirements for an Investigational New
Drug filing, we assessed the safety of tumor-targeted interleukin-12 (ttIL-12) when administered
by EGT in C3H/HeJ mice by identifying an initial safe dose for human dose escalation schemes,
toxicity target organs, markers of toxicity, and toxicity reversibility. Dystrophic cardiac
calcification in older, 5 ìg ttIL-12-treated mice was the only serious toxicity. Based on these
results and the lack of any effect on wound healing when combined with surgery, low-intensity
EGT with ttIL-12 appears to be safe and well tolerated as both a single treatment modality and
when combined with surgical tumor resection.
| Identifer | oai:union.ndltd.org:LSU/oai:etd.lsu.edu:etd-11172010-085322 |
| Date | 19 November 2010 |
| Creators | Reed, Scott Douglas |
| Contributors | Li, Shulin, Sehgal, Inder, Morgan, Timothy, Wakamatsu, Nobuko, Prosanta Chakrabarty |
| Publisher | LSU |
| Source Sets | Louisiana State University |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.lsu.edu/docs/available/etd-11172010-085322/ |
| Rights | unrestricted, I hereby certify that, if appropriate, I have obtained and attached herein a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to LSU or its agents the non-exclusive license to archive and make accessible, under the conditions specified below and in appropriate University policies, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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