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

Abstract

On the basis of superior outcomes from electrochemogenetherapy (ECGT) compared with electrochemotherapy in mice, we determined the efficacy of ECGT applied to spontaneous canine neoplasms. Intralesional bleomycin (BLM) and feline interleukin-12 DNA injection combined with translesional electroporation resulted in complete cure of two recurrent World Health Organization stage T 2b N 0 M 0 oral squamous cell carcinomas (SCCs) and one T 2 N 0 M 0 acanthomatous ameloblastoma. Three remaining dogs, which had no other treatment options, had partial responses to ECGT; one had mandibular T 3b N 2b M 1 melanoma with pulmonary and lymph node metastases; one had cubital T 3 N 0 M 1 histiocytic sarcoma with spleen metastases; and one had soft palate T 3 N 0 M 0 fibrosarcoma. 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 4 months after the only treatment. The dog with T 3 N 0 M 0 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 seems to be a safe and resulted in complete responses in SCC and acanthomatous ameloblastoma.

Electroporation increases antitumoral efficacy of the bcl-2 antisense G3139 and chemotherapy in a human melanoma xenograft

“…However, this mechanism leads to the apoptotic death of tumor cells resulting in a high tumoricidal effect with good cosmetic results (minimal scar tissue formation in the treated patients). A final advantage of electrochemotherapy is the possible modulation of the immune system, probably through the uncovering of cancer antigens, as suggested by studies showing a synergy with interleukin 2 or 12 [51,52]. Furthermore, our investigations on companion animals with spontaneous cancer evidenced a clonal selection of the neoplasms treated with electrochemotherapy and longer survival in dogs with melanoma that developed vitiligo-like lesions at the tumor site after electroporation [53].…”

CD8+T cell–specific induction of NKG2D receptor by doxorubicin plus interleukin-12 and its contribution to CD8+T cell accumulation in tumors

“…This procedure yielded a blood IL-12 level greater than 100 pg/mL [47]. The electroporation parameters for intramuscular injection, which had previously been identified as optimal, were set at 350 V/cm and 20 ms pulse duration for 2 pulses [46].…”

Intratumoural interleukin 12 gene therapy stimulates the immune system and decreases angiogenesis in dogs with spontaneous cancer

“…Once the pDNA reaches the cell's nucleus, the production of the protein encoded by the plasmid ensues . In vivo electroporation does not cause any severe adverse events, and several canine and human clinical trials showed the safety and clinical efficacy of electroporation‐mediated intratumoural delivery of a pDNA encoding IL‐12 . Those studies present evidence that it is possible to overcome local suppressor pathways in tumours and tip the balance in favour of an antitumour immune response.…”