In vivo electroporation of plasmids encoding GM-CSF or interleukin-2 into existing B16 melanomas combined with electrochemotherapy induces long-term antitumour immunity.
When cancer cells, including melanoma cells, are genetically altered to secrete cytokines, irradiated and injected into subjects, long-term antitumour immunity is induced. Optimally, existing melanomas induced to produce cytokines in vivo could stimulate this same immune response. Although in vivo electroporation enhances plasmid expression, electroporation of plasmids encoding granulocyte-monocyte colony stimulating factor (GM-CSF) and interleukin-2 (IL2) into B16 mouse melanomas did not significantly alter tumour growth at the concentration tested. Electrochemotherapy, which causes short-term, complete regressions of treated tumour but no resistance to challenge, was combined with plasmid delivery. The combination treatment resulted in the induction of long-term immunity to recurrence and resistance to challenge in up to 25% of mice.
Heller
L
L
Center for Molecular Delivery, University of South Florida, Tampa 33612, USA. lheller@com1.med.usf.edu
Pottinger
C
C
Jaroszeski
M J
MJ
Gilbert
R
R
Heller
R
R
D000818:Animals; D019496:Cancer Vaccines / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D016207:Cytokines / Q000096:biosynthesis; D004247:DNA / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D018274:Electroporation / Q000379:methods*; D004797:Enzyme-Linked Immunosorbent Assay; D015316:Genetic Therapy / Q000379:methods*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000378:metabolism*; D007376:Interleukin-2 / Q000235:genetics / Q000378:metabolism*; D008156:Luciferases / Q000378:metabolism; D008546:Melanoma, Experimental / Q000378:metabolism*; D051379:Mice; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000517:prevention & control* / Q000628:therapy*; D010957:Plasmids / Q000378:metabolism*; D012008:Recurrence; D013997:Time Factors
D019496:Cancer Vaccines; D016207:Cytokines; D007376:Interleukin-2; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D004247:DNA; D008156:Luciferases