ID: 2190

• Title:
  Comparison of intratumoral and peritumoral application of IL-12 in combination with electrochemotherapy for the treatment of spontaneous canine mast cell tumors
  
  Authors:
  

  Lampreht Tratar, Ursa 
  Milevoj, Nina, 
  Cemazar, Maja
  Znidar, Katarina 
  Ursic Valentinuzzi, Katja 
  Brozic, Andreja 
  Tomsic, Katerina 
  Sersa, Gregor 
  Tozon, Natasa
  

  
  
  Abstract:
  Ursa Lampreht Tratar1,2, Nina Milevoj2, Maja Cemazar1,3 , Katarina Znidar1, Katja Ursic Valentinuzzi1,4, Andreja Brozic1, Katerina Tomsic2, Gregor Sersa1,5, Natasa Tozon2
  
  
  
  1Department of Experimental Oncology, Institute of Oncology Ljubljana, Zaloska 2, 1000, Ljubljana, Slovenia
  
  2Veterinary Faculty, University of Ljubljana, Gerbiceva 60, Ljubljana, Slovenia
  
  3Faculty of Health Sciences, University of Primorska, Polje 42, Izola, 6310, Slovenia
  
  4Biotechnical Faculty, University of Ljubljana, Jamnikarjeva ulica 101, SI-1000 Ljubljana, Slovenia
  
  5Faculty of Health Sciences, University of Ljubljana, Zdravstvena pot 5, 1000, Ljubljana, Slovenia
  
  
  
  The combination of electrochemotherapy (ECT) and interleukin-12 (IL -12) gene electrotransfer (GET) has already been used in clinical trials in dogs for the treatment of various histological types of spontaneous tumours. The results of these studies show that the treatment is safe and effective. However, in these clinical trials IL -12 GET was administered either intratumorally (i.t.) or peritumorally (peri.t.). The aim of this clinical trial was therefore to compare the two IL -12 GET routes of administration in combination with ECT and their contribution to the enhanced ECT response. Seventy-seven dogs with spontaneous mast cell tumours (MCTs) were divided into three groups: one was treated with a combination of ECT+GET peri. t. (29 dogs), the second with the combination of ECT+GET i.t. (30 dogs) and the third with ECT alone (18 dogs). In addition, immunohistochemical analysis of tumour samples before treatment and flow cytometry of peripheral blood mononuclear cells (PBMCs) before and after treatment were performed to determine immunological aspects of the treatment. The results showed that local tumour control was significantly better in the ECT+GET i.t. group (p < 0.050) than in the ECT+GET peri.t. or ECT groups. In addition, the disease-free interval (DFI) and progression-free survival (PFS) were significantly longer in the ECT+GET i.t. group than in the other two groups (p < 0.050). The local tumour response, DFI and PFS data were consistent with the immunological tests, as we detected an increased percentage of antitumour immune cells in the blood after treatment in the ECT+GET i.t. group, also indicating the induction of a systemic immune response. Furthermore, we did not observe any adverse severe or long-lasting side effects. Finally, due to the more pronounced local response after ECT+GET i.t., we suggest that the assessment of response to treatment should be performed at least two months after treatment, which is in line with the iRECIST criteria.
  
  
  
  Keywords:
  electrochemotherapy, gene electrotransfer, interleukin-12, dog, mast cell tumor
  
  Refs:
  
  
  Topic 1:
  6. Cancer treatment and tumor ablation
  
  Topic 2:
  12. Biomedical applications