Document Type
Article
Publication Date
2002
Publication Title
Molecular Therapy
Volume
5
Issue
6
Pages
668-675
DOI
10.1006/mthe.2002.0601
Abstract
Interleukin-12 (IL-12) has been used in numerous immunotherapy protocols against melanoma. However, delivery of IL-12 in the form of recombinant protein can result in severe toxicity, and gene therapy has had limited success against B16.F10 murine melanoma. The purpose of this study was to examine the effectiveness of in vivo electroporation for the delivery of plasmid DNA encoding IL-12 as an antitumor agent against B16.F10 melanoma. We treated mice bearing established B16.F10 melanoma tumors with intratumoral (i.t.) or intramuscular (i.m.) injections of a plasmid encoding IL-12, followed by in vivo electroporation. For i.t. treatments, we used an applicator containing six penetrating electrodes to deliver 1500-V/cm, 100-micros pulses. We administered i.m. pulses with an applicator containing four penetrating electrodes delivering 100-V/cm, 20-ms pulses. The i.t. treatment resulted in the cure of 47% of tumor-bearing mice, and 70% of cured mice were resistant to challenge with B16.F10 cells. The i.m. treatment did not result in tumor regression. We found that i.t. treatment resulted in increased levels of IL-12 and interferon-γ (IFN-γ) within the tumors, the influx of lymphocytes into the tumors, and reduction in vascularity. Neither i.m. nor i.t. treatment was successful against B16.F10 tumors in a nude mouse model, supporting a role for T cells in regression of this tumor model.
Original Publication Citation
Lucas, M. L., Heller, L., Coppola, D., & Heller, R. (2002). IL-12 plasmid delivery by in vivo electroporation for the successful treatment of established subcutaneous B16.F10 melanoma. Molecular Therapy, 5(6), 668-675. doi:10.1006/mthe.2002.0601
Repository Citation
Lucus, M. Lee; Heller, Loree; Coppola, Domenico; and Heller, Richard, "IL-12 Plasmid Delivery by in Vivo Electroporation for the Successful Treatment of Established Subcutaneous B16.F10 Melanoma" (2002). Bioelectrics Publications. 112.
https://digitalcommons.odu.edu/bioelectrics_pubs/112
ORCID
0000-0001-8084-0787 (Heller, L.), 0000-0003-1899-3859 (Heller, R.)