Co-delivery of cancer-associated antigen and Toll-like receptor 4 ligand in PLGA nanoparticles induces potent CD8+ T cell-mediated anti-tumor immunity.
The purpose of this study was to evaluate the efficacy of poly(lactic-co-glycolic acid) (PLGA)-based vaccines in breaking immunotolerance to cancer-associated self-antigens. Vaccination of mice bearing melanoma B16 tumors with PLGA nanoparticles (NP) co-encapsulating the poorly immunogenic melanoma antigen, tyrosinase-related protein 2 (TRP2), along with Toll-like receptor (TLR) ligand (7-acyl lipid A) was examined. Remarkably, this vaccine was able to induce therapeutic anti-tumor effect. Activated TRP2-specific CD8 T cells were capable of interferon (IFN)-gamma secretion at lymph nodes and spleens of the vaccinated mice. More importantly, TRP2/7-acyl lipid A-NP treated group has shown immunostimulatory milieu at the tumor microenvironment, as evidenced by increased level of pro-inflammatory cytokines compared to control group. These results support the potential use of PLGA nanoparticles as competent carriers for future cancer vaccine formulations.
Hamdy
Samar
S
Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta T6G 2N8, Canada.
Molavi
Ommoleila
O
Ma
Zengshuan
Z
Haddadi
Azita
A
Alshamsan
Aws
A
Gobti
Zahra
Z
Elhasi
Sara
S
Samuel
John
J
Lavasanifar
Afsaneh
A
D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D019496:Cancer Vaccines / Q000276:immunology*; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D004337:Drug Carriers / Q000627:therapeutic use; D007371:Interferon-gamma / Q000276:immunology; D019746:Intramolecular Oxidoreductases / Q000276:immunology; D019344:Lactic Acid / Q000008:administration & dosage / Q000627:therapeutic use*; D008050:Lipid A / Q000276:immunology; D008546:Melanoma, Experimental / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000008:administration & dosage / Q000627:therapeutic use; D011100:Polyglycolic Acid / Q000008:administration & dosage / Q000627:therapeutic use*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D051197:Toll-Like Receptor 4 / Q000276:immunology*
D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D004337:Drug Carriers; D008050:Lipid A; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D007371:Interferon-gamma; D019746:Intramolecular Oxidoreductases; C042501:dopachrome isomerase