ID: 2181

• Title:
  Treatment of Skin Tumors with Intratumoral Interleukin 12 Gene Electrotransfer in the Head and Neck Region: A Phase I Clinical Trial
  
  Authors:
  

  Sersa, Gregor - Institute of Oncology Ljubljana
  Strojan, Primoz - Institute of Oncology Ljubljana
  Groselj, Ales - University Medical Center Ljubljana 
  Jamsek, Crt -  University Medical Center Ljubljana
  Jesenko, Tanja - Institute of Oncology Ljubljana 
  Bosnjak, Masa - Institute of Oncology Ljubljana 
  Markelc, Bostjan - Institute of Oncology Ljubljana
  Gasljevic, Gorana - Institute of Oncology Ljubljana 
  Cemazar, Maja - Institute of Oncology Ljubljana 

  
  
  Abstract:
  Immunotherapies with monoclonal antibodies (checkpoint inhibitors) are currently being intensively researched and have resulted in excellent responses in many cases of various tumors. Another potential approach to immunotherapy is the targeted intratumoral administration of interleukin 12 (IL -12), a cytokine with proven anti-tumor activity. Due to its immunomodulatory effect, it can be used as an immunostimulatory component for in situ vaccination of local ablative therapies. We have developed a phIL12 plasmid without antibiotic resistance markers that contains a transgene for the human IL -12 p70 protein. The plasmid can be introduced intratumorally by gene electrotransfer. In gene electrotransfer, electric pulses are applied to the tumor to deliver the plasmid DNA into the cells. Based on nonclinical studies of safety, pharmacokinetics, pharmacodynamics, tolerability, and immunogenicity, a phase I clinical trial of phIL12 gene electrotransfer was conducted (ISRCTN15479959, ClinicalTrials NCT05077033). The primary objective of the study was to evaluate the safety and tolerability of phIL12 gene electrotransfer in the treatment of basal cell carcinoma in patients with operable tumors of the head and neck. The study, an exploratory, dose-escalating Phase I trial, enrolled 9 patients in three dose-escalating cohorts. Treatment consisted of injection of the plasmid followed by application of electric pulses to the tumors. Patients were monitored for 30 days, with tumors removed if a complete response was not achieved. All three cohorts of patients completed the study. No adverse effects or treatment-related toxicities were observed, and treatment was well tolerated by patients. Biological samples collected during the study will be analyzed and the biological activity of the transfected plasmid will be determined. The results of this study protocol provide the basis for the use of phIL12 gene electrotransfer as an adjuvant therapy to local ablative therapies to enhance their local effect and elicit a systemic response.
  
  Keywords:
  interleukin-12, immuno therapy, gene therapy, gene electrotransfer
  
  Refs:
  
  
  Topic 1:
  6. Cancer treatment and tumor ablation
  
  Topic 2:
  12. Biomedical applications