Bleomycin/interleukin-12 electrochemogene therapy for treating naturally occurring spontaneous neoplasms in dogs

Abstract

Based on superior outcomes from electrochemogene therapy (ECGT) compared to electrochemotherapy (ECT)in mice, we determined the efficacy of ECGT applied to spontaneous canine neoplasms. Intralesional bleomycin (BLM) and feline interleukin-12 DNA (fIL-12 DNA) injection combined with trans-lesional electroporation resulted in complete cure of two recurrent World Health Organization (WHO) stageT2bN0M0 oral squamous cell carcinomas (SCCs)and one T2N0M0acanthomatous ameloblastoma. Three remaining dogs, which had no other treatment options, had partial responses to ECGT; one had mandibular T3bN2bM1 melanoma with pulmonary and lymph node metastases; one had cubital T3N0M1 histiocytic sarcoma with spleen metastases; and one had soft palate T3N0M0fibrosarcoma. The melanoma dog had decrease in the size of the primary tumor before recrudescence and euthanasia. The histiocytic sarcoma dog had resolution of the primary tumor, but was euthanized because of metastases four months after the only treatment. The dog with T 3N0M0 fibrosarcoma had tumor regression with recrudescence. Treatment was associated with minimal side effects and was easy to perform; was associated with repair of bone lysis in cured dogs; improved quality of life for dogs with partial responses; and extended overall survival time. ECGT appears to be a safe and resulted in complete responses in SCC and acanthomatous ameloblastoma.

Plasmid DNA Gene Therapy by Electroporation: Principles and Recent Advances

“…In another study, delivery of plasmid DNA encoding K-ras-specific microRNAs by electroporation inhibited colorectal adenocarcinoma cell growth in vitro and in vivo [81]. The combination of bleomycin and IL-12 gene injection with electroporation was evaluated for treating neoplasms in dogs [82], and this electrochemogene therapy resulted in effective immune responses in squamous cell carcinomas and acanthomatous ameloblastomas.…”

Cytokine-enhanced vaccine and suicide gene therapy as surgery adjuvant treatments for spontaneous canine melanoma: 9 years of follow-up

“…5 Different gene therapy approaches have been reported for canine spontaneous melanoma such as: (i) ex vivo human interleukin-2 (hIL-2) producing xenogeneic cells, 6 human granulocytemacrophage colony-stimulating factor (hGM-CSF) producing autologous tumor cells, 7 human gp100 producing allogeneic tumor cells; 8 and (ii) in vivo gene transfer of enterotoxin-B plus GM-CSF, 9 xenogeneic human 10 or murine 11 tyrosinase, human FasL, 12 IL-12 (ref. 13) and CD40 ligand. 14 About 80% of the veterinary cancer gene therapy trials on patients with spontaneous tumors could be classified as immunogene therapy and were performed with non-viral vectors.…”

IL-12 based gene therapy in veterinary medicine

“…Furthermore, successful sequencing of the canine genome [51] has led to characterization of a variety of genetic disorders in dogs, such as hemophilia, mucopolisaharidosis VII, and various cardiovascular diseases and cancers. A number of clinical studies have also been initiated for the treatment of canine cancers, using different therapeutic genes, such as Fas ligand, bacterial superantigens and cytokines, including GM-CFS, IL-2 and IL-12 [52-58]. Another palliative approach to tumor-bearing dogs employed gene therapy with gene encoding growth hormone releasing hormone in order to ameliorate tumor cachexia and improve the general clinical status of patients [59].…”

“…In dogs, IL-12 EGT has been investigated on a number of different induced and spontaneously occurring tumors [57,58,66,67]. In these studies, either human or feline IL-12 was used as a therapeutic gene due to the non-availability of canine IL-12 and high homology between canine and these two cytokines [68].…”