Nonviral therapeutic cell vaccine mediates potent antitumor effects.
Therapeutic vaccination of mice bearing melanoma tumors with our genetically modified tumor cells, via DOTAP/GM-CSF lipoplexes, results in >85% tumor growth inhibition. These fresh transfected cells (irradiated, frozen and thawed) are able to produce high amounts of GM-CSF transgene (>200 ng/10(6) cells/24 h). After vaccination, significant increases (>eight-fold) in specific antitumor membrane protein IgG1 and IgG2a are obtained only in groups vaccinated with GM-CSF-producing cells, where also the highest rates of tumor inhibition, and significantly delayed mice death (P<0.05), are observed. The antitumor response obtained is long-lasting in survivors (GM-CSF-group) from 6 months after the first tumor challenge, and a full 100% of mice survived to a second tumor challenge. All these results suggest that antitumor cell vaccines engineered by nonviral procedures are suitable for use as therapeutic vaccines with potential clinical applications.
Gene Therapy Group, Department of Pharmacology, School of Medicine, Avda. de Blasco Ibáñez 15, Valencia 46010, Spain.
Inés
I
Moret-Tatay
Isaías
I
Sanmartín
Francisco M
FM
Marco
Joaquín
J
Díaz
Salvador F
SF
Aliño
D000818:Animals; D000912:Antibodies, Neoplasm / Q000097:blood; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology; D019496:Cancer Vaccines / Q000276:immunology* / Q000627:therapeutic use*; D002462:Cell Membrane / Q000276:immunology; D005229:Fatty Acids, Monounsaturated; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000097:blood; D007167:Immunotherapy / Q000379:methods*; D008297:Male; D008546:Melanoma, Experimental / Q000276:immunology / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D000644:Quaternary Ammonium Compounds; D016019:Survival Analysis; D014162:Transfection
D000912:Antibodies, Neoplasm; D000970:Antineoplastic Agents; D019496:Cancer Vaccines; D005229:Fatty Acids, Monounsaturated; D007074:Immunoglobulin G; D000644:Quaternary Ammonium Compounds; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; C070046:1,2-dioleoyloxy-3-(trimethylammonium)propane