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Electrochemotherapy and Gene Electrotransfer in Veterinary Oncology

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Handbook of Electroporation

Abstract

Veterinary medicine has become an important translational bridge from in vitro and preclinical studies to human medicine, offering invaluable model for research in naturally occurring diseases and therefore providing vital data which cannot be gained from strictly experimental animal models. This is especially true for investigating novel approaches to cancer treatment. Electrochemotherapy and gene electrotransfer are two such novel treatment options in both human and veterinary clinical oncology. Current research shows that electrochemotherapy has excellent local ablative effect on treated tumors. However, its major drawback lies in its inability for any type of systemic antitumor effect. Therefore, one possibility to boost its effect is combining electrochemotherapy with systemic immunomodulatory effects of interleukin-12 (IL-12) gene electrotransfer, since both use the same platform technology, electroporation. In veterinary medicine, the combined treatment was successfully used in different types of tumors in dogs and horses, providing excellent local antitumor control with indications of systemic effects of such treatments, clinically seen as prolongation of treated patients’ lifespan, distant effect on untreated tumors, lymph node metastases, and regression of invasive tumor growth. Furthermore, immunologic studies show that this type of treatment causes systemic induction of patient’s immune response as seen from flow cytometry of treated patients’ blood showing temporary increase of circulating cluster of differentiation 8 positive (CD8+) cells after each therapeutic session. With use of IL-12-based gene therapy, several important safety aspects should be observed, mainly possible IL-12 toxicity and environmental safety of this type of therapy, regarding possible shedding of antibiotic resistance genes into environmental bacteria.

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References

  • Calvet CY, Famin D, André FM, Mir LM (2014) Electrochemotherapy with bleomycin induces hallmarks of immunogenic cell death in murine colon cancer cells. Oncoimmunology 3:e28131

    Article  Google Scholar 

  • Cemazar M, Miklavcic D, Scancar J, Dolzan V, Golouh R, Sersa G (1999) Increased platinum accumulation in SA-1 tumour cells after in vivo electrochemotherapy with cisplatin. Br J Cancer 79:1386–1391

    Article  Google Scholar 

  • Cemazar M, Tamzali Y, Sersa G, Tozon N, Mir LM, Miklavcic D, Lowe R, Teissie J (2008) Electrochemotherapy in veterinary oncology. J Vet Intern Med 22:826–831. doi:10.1111/j.1939-1676.2008.0117.x

    Article  Google Scholar 

  • Cemazar M, Sersa G, Pavlin D, Tozon N (2011) Intramuscular IL-12 electrogene therapy for treatment of spontaneous canine tumors. In: You Y (ed) Targets in gene therapy. InTech, Rijeka, pp 299–321

    Google Scholar 

  • Cemazar M, Ambrozic Avgustin J, Pavlin D, Sersa G, Poli A, Krhac Levacic A, Tesic N, Lampreht Tratar U, Rak M, Tozon N (2016) Efficacy and safety of electrochemotherapy combined with peritumoral IL-12 gene electrotransfer of canine mast cell tumours. Vet Comp Oncol. doi:10.1111/vco.12208

    Google Scholar 

  • Chou PC, Chuang TF, Jan TR, Gion HC, Huang YC, Lei HJ, Chen WY, Chu RM (2009) Effects of immunotherapy of IL-6 and IL-15 plasmids on transmissible venereal tumor in beagles. Vet Immunol Immunopathol 130:25–34. doi:10.1016/j.vetimm.2009.01.002

    Article  Google Scholar 

  • Cutrera J, King G, Jones P, Kicenuik K, Gumpel E, Xia X, Li S (2015) Safe and effective treatment of spontaneous neoplasms with interleukin 12 electro-chemo-gene therapy. J Cell Mol Med 19:664–675

    Article  Google Scholar 

  • Daud AI, DeConti RC, Andrews S, Urbas P, Riker AI, Sondak VK, Munster PN, Sullivan DM, Ugen KE, Messina JL, Heller R (2008) Phase I trial of interleukin-12 plasmid electroporation in patients with metastatic melanoma. J Clin Oncol 26:5896–5903. doi:10.1200/JCO.2007.15.6794

    Article  Google Scholar 

  • Draghia-Akli R, Hahn KA, King GK, Cummings KK, Carpenter RH (2002) Effects of plasmid-mediated growth hormone-releasing hormone in severely debilitated dogs with cancer. Mol Ther 6:830–836

    Article  Google Scholar 

  • Easty AC, Coakley N, Cheng R, Cividino M, Savage P, Tozer R, White RE (2015) Safe handling of cytotoxics: guideline recommendations. Curr Oncol 22:e27–e37. doi:10.3747/co.21.2151

    Article  Google Scholar 

  • Forde PF, Sadadcharam M, Bourke MG, Conway TA, Guerin SR, de Kruijf M, O'Sullivan GC, Impellizeri J, Clover AJ, Soden DM (2016) Preclinical evaluation of an endoscopic electroporation system. Endoscopy 48:477–483. doi:10.1055/s-0042-101343

    Article  Google Scholar 

  • Fridman WH, Pagès F, Sautès-Fridman C, Galon J (2012) The immune contexture in human tumours: impact on clinical outcome. Nat Rev Cancer 12:298–306

    Article  Google Scholar 

  • Gavazza A, Lubas G, Fridman A, Peruzzi D, Impellizeri JA, Luberto L, Marra E, Roscilli G, Ciliberto G, Aurisicchio L (2013) Safety and efficacy of a genetic vaccine targeting telomerase plus chemotherapy for the therapy of canine B-cell lymphoma. Hum Gene Ther 24:728–738. doi:10.1089/hum.2013.112

    Article  Google Scholar 

  • Heller L, Merkler K, Westover J, Cruz Y, Coppola D, Benson K, Daud A, Heller R (2006) Evaluation of toxicity following electrically mediated interleukin-12 gene delivery in a B16 mouse melanoma model. Clin Cancer Res 12:3177–3183

    Article  Google Scholar 

  • Jacobson JM, Zheng L, Wilson CC, Tebas P, Matining RM, Egan MA, Eldridge J, Landay AL, Clifford DB, Luetkemeyer AF, Tiu J, Martinez AL, Janik J, Spitz TA, Hural J, McElrath J, Frahm N, ACTG A5281 Protocol Team (2016) The safety and immunogenicity of an interleukin-12-enhanced multiantigen DNA vaccine delivered by electroporation for the treatment of HIV-1 infection. J Acquir Immune Defic Syndr 71:163–171. doi:10.1097/QAI.0000000000000830

    Article  Google Scholar 

  • Lucas ML, Heller R (2003) IL-12 gene therapy using an electrically mediated nonviral approach reduces metastatic growth of melanoma. DNA Cell Biol 22:755–763

    Article  Google Scholar 

  • Mali B, Jarm T, Snoj M, Sersa G, Miklavcic D (2013) Antitumor effectiveness of electrochemotherapy: a systematic review and meta-analysis. Eur J Surg Oncol 39:4–16. doi:10.1016/j.ejso.2012.08.016

    Article  Google Scholar 

  • Marčan M, Pavliha D, Kos B, Forjanič T, Miklavčič D (2015) Web-based tool for visualization of electric field distribution in deep-seated body structures and planning of electroporation-based treatments. Biomed Eng Online 14(Suppl 3):S4

    Article  Google Scholar 

  • O’Neill K, Guth A, Biller B, Elmslie R, Dow S (2009) Changes in regulatory T cells in dogs with cancer and associations with tumor type. J Vet Intern Med 23:875–881

    Article  Google Scholar 

  • Pavlin D, Cemazar M, Kamensek U, Tozon N, Pogacnik A, Sersa G (2009) Local and systemic antitumor effect of intratumoral and peritumoral IL-12 electrogene therapy on murine sarcoma. Cancer Biol Ther 8:2114–2122

    Article  Google Scholar 

  • Pavlin D, Cemazar M, Cör A, Sersa G, Pogacnik A, Tozon N (2011) Electrogene therapy with interleukin-12 in canine mast cell tumors. Radiol Oncol 45:31–39

    Article  Google Scholar 

  • Piras LA, Riccardo F, Iussich S, Maniscalco L, Gattino F, Martano M, Morello E, Lorda Mayayo S, Rolih V, Garavaglia F, De Maria R, Lardone E, Collivignarelli F, Mignacca D, Giacobino D, Ferrone S, Cavallo F, Buracco P (2016) Prolongation of survival of dogs with oral malignant melanoma treated by en bloc surgical resection and adjuvant CSPG4-antigen electrovaccination. Vet Comp Oncol. doi:10.1111/vco.12239

    Google Scholar 

  • Reed SD, Fulmer A, Buckholz J, Zhang B, Cutrera J, Shiomitsu K, Li S (2010) Bleomycin/interleukin-12 electrochemogene therapy for treating naturally occurring spontaneous neoplasms in dogs. Cancer Gene Ther 17:457–464. doi:10.1038/cgt.2010.6

    Article  Google Scholar 

  • Sersa G, Teissie J, Cemazar M, Signori E, Kamensek U, Marshall G, Miklavcic D (2015) Electrochemotherapy of tumors as in situ vaccination boosted by immunogene electrotransfer. Cancer Immunol Immunother 64:1315–1327. doi:10.1007/s00262-015-1724-2

    Article  Google Scholar 

  • Tamzali Y, Couderc B, Rols MP, Golzio M, Teissie J (2007) Equine cutaneous tumors treatment by electro-chemo-immuno-geno-therapy. In: Jarm T, Kramar P, Zupanic A (eds) IFMBE proceedings 11th Mediterranean conference on medical and biological engineering and computing. Springer, Berlin, p 630

    Google Scholar 

  • Tannenbaum CS, Tubbs R, Armstrong D, Finke JH, Bukowski RM, Hamilton TA (1998) The CXC chemokines IP-10 and Mig are necessary for IL-12-mediated regression of the mouse RENCA tumor. J Immunol 161:927–932

    Google Scholar 

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Correspondence to Darja Pavlin .

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Pavlin, D., Čemažar, M., Serša, G., Tamzali, Y., Tozon, N. (2016). Electrochemotherapy and Gene Electrotransfer in Veterinary Oncology. In: Miklavcic, D. (eds) Handbook of Electroporation. Springer, Cham. https://doi.org/10.1007/978-3-319-26779-1_108-1

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  • DOI: https://doi.org/10.1007/978-3-319-26779-1_108-1

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  • Publisher Name: Springer, Cham

  • Online ISBN: 978-3-319-26779-1

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