Intratumoral DNA electroporation induces anti-tumor immunity  and tumor regression.
In situ expression of a foreign antigen and an immune-modulating cytokine by intratumoral DNA electroporation was tested as a cancer therapy regimen. Transgene expression in the tumors was sustained for 2-3 weeks after intratumoral electroporation with mammalian expression plasmid containing firefly luciferase cDNA. Electroporation with cDNA encoding tetanus toxin fragment C (TetC) induced tetanus toxin-binding antibody, demonstrating immune recognition of the transgene product. Intratumoral electroporation with TetC and IL-12 cDNA after mice were treated with CD25 mAb to remove regulatory T cells induced IFN-gamma producing T-cell response to tumor-associated antigen, heavy inflammatory infiltration, regression of established tumors and immune memory to protect mice from repeated tumor challenge. Intratumoral expression of immune-modulating molecules may be most suitable in the neoadjuvant setting to enhance the therapeutic efficacy and provide long-term protection.
Radkevich-Brown
Olga
O
Karmanos Cancer Institute, Wayne State University, Detroit, MI 48201, USA.
Piechocki
Marie P
MP
Back
Jessica B
JB
Weise
Amy M
AM
Pilon-Thomas
Shari
S
Wei
Wei-Zen
WZ
D000818:Animals; D019496:Cancer Vaccines / Q000276:immunology* / Q000627:therapeutic use*; D018274:Electroporation; D015870:Gene Expression; D007156:Immunologic Memory; D018664:Interleukin-12 / Q000235:genetics; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D009369:Neoplasms / Q000276:immunology* / Q000628:therapy*; D010446:Peptide Fragments / Q000235:genetics; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D013744:Tetanus Toxin / Q000235:genetics; D014162:Transfection; D019076:Transgenes; D019444:Vaccines, DNA / Q000276:immunology* / Q000627:therapeutic use*
D019496:Cancer Vaccines; D010446:Peptide Fragments; D013744:Tetanus Toxin; D019444:Vaccines, DNA; C040635:tetanus toxin fragment C; D018664:Interleukin-12