IL-2 plasmid electroporation: from preclinical studies to phase I clinical trial.
Electroporation (EP)-assisted intralesional delivery of Interleukin-2 (IL-2) plasmid (pDNA) has the potential to increase the local concentration of the expressed cytokine for an extended time in the injected tumors while minimizing its systemic concentration, in comparison with systemic delivery of the recombinant cytokine. Nonclinical Investigational New Drug application-enabling studies were performed in mice to evaluate the effect of intratumoral administration of murine IL-2 pDNA on local expression and systemic distribution of IL-2 transgene as well as the inhibition of established tumor growth. The safety of repeated administrations of a human IL-2 pDNA product candidate with EP was evaluated in rats. Following the nonclinical safety and efficacy studies, a human IL-2 pDNA product candidate intralesionally administered with EP to metastatic melanoma patients is currently being investigated in a phase I clinical trial.
Horton
Holly M
HM
Vical, Inc., San Diego, CA, USA.
Lalor
Peggy A
PA
Rolland
Alain P
AP
D000818:Animals; D045744:Cell Line, Tumor; D004274:DNA, Recombinant / Q000008:administration & dosage / Q000235:genetics; D053672:Electrochemotherapy / Q000379:methods*; D015316:Genetic Therapy / Q000009:adverse effects / Q000379:methods*; D006801:Humans; D007376:Interleukin-2 / Q000008:administration & dosage / Q000235:genetics*; D008545:Melanoma / Q000556:secondary / Q000628:therapy; D008546:Melanoma, Experimental / Q000628:therapy; D051379:Mice; D008811:Mice, Inbred DBA; D010957:Plasmids / Q000008:administration & dosage* / Q000235:genetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000235:genetics; D012449:Safety
D004274:DNA, Recombinant; D007376:Interleukin-2; D011994:Recombinant Proteins