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.
Moret-Tatay
Inés
I
Gene Therapy Group, Department of Pharmacology, School of Medicine, Avda. de Blasco Ibáñez 15, Valencia 46010, Spain.
Sanmartín
Isaías
I
Marco
Francisco M
FM
Díaz
Joaquín
J
Aliño
Salvador F
SF
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