title: Viral-mimicking protein nanoparticle vaccine for eliciting anti-tumor responses.
abstract: The immune system is a powerful resource for the eradication of cancer, but to overcome the low immunogenicity of tumor cells, a sufficiently strong CD8(+) T cell-mediated adaptive immune response is required. Nanoparticulate biomaterials represent a potentially effective delivery system for cancer vaccines, as they can be designed to mimic viruses, which are potent inducers of cellular immunity. We have been exploring the non-viral pyruvate dehydrogenase E2 protein nanoparticle as a biomimetic platform for cancer vaccine delivery. Simultaneous conjugation of a melanoma-associated gp100 epitope and CpG to the E2 nanoparticle (CpG-gp-E2) yielded an antigen-specific increase in the CD8(+) T cell proliferation index and IFN-γ secretion by 1.5-fold and 5-fold, respectively, compared to an unbound peptide and CpG formulation. Remarkably, a single nanoparticle immunization resulted in a 120-fold increase in the frequency of melanoma epitope-specific CD8(+) T cells in draining lymph nodes and a 30-fold increase in the spleen, relative to free peptide with free CpG. Furthermore, in the very aggressive B16 melanoma murine tumor model, prophylactic immunization with CpG-gp-E2 delayed the onset of tumor growth by approximately 5.5 days and increased animal survival time by approximately 40%, compared to PBS-treated animals. These results show that by combining optimal particle size and simultaneous co-delivery of molecular vaccine components, antigen-specific anti-tumor immune responses can be significantly increased.
authors.affiliation: Department of Chemical Engineering and Materials Science, University of California, Irvine, CA 92697, USA.
authors.forename: Nicholas M
authors.initials: NM
authors.lastname: Molino
authors.affiliation: Department of Chemical Engineering and Materials Science, University of California, Irvine, CA 92697, USA.
authors.forename: Medea
authors.initials: M
authors.lastname: Neek
authors.affiliation: Department of Medicine, University of California, Irvine, CA 92697, USA.
authors.forename: Jo Anne
authors.initials: JA
authors.lastname: Tucker
authors.affiliation: Department of Medicine, University of California, Irvine, CA 92697, USA; Chao Family Comprehensive Cancer Center, University of California, Irvine, CA 92697, USA; Institute for Immunology, University of California, Irvine, CA 92697, USA.
authors.forename: Edward L
authors.initials: EL
authors.lastname: Nelson
authors.affiliation: Department of Chemical Engineering and Materials Science, University of California, Irvine, CA 92697, USA; Chao Family Comprehensive Cancer Center, University of California, Irvine, CA 92697, USA; Department of Biomedical Engineering, University of California, Irvine, CA 92697, USA. Electronic address: wangsw@uci.edu.
authors.forename: Szu-Wen
authors.initials: SW
authors.lastname: Wang
mesh_terms: D000818:Animals; D032701:Biomimetics; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use*; D002478:Cells, Cultured; D018899:CpG Islands; D016503:Drug Delivery Systems; D000939:Epitopes / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007114:Immunization; D007371:Interferon-gamma / Q000276:immunology; D008546:Melanoma, Experimental / Q000276:immunology / Q000517:prevention & control*; D051379:Mice; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000008:administration & dosage / Q000627:therapeutic use*; D011768:Pyruvate Dehydrogenase Complex / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use*; D058951:gp100 Melanoma Antigen / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use*
chemical_list: D019496:Cancer Vaccines; D000939:Epitopes; D011768:Pyruvate Dehydrogenase Complex; D058951:gp100 Melanoma Antigen; D007371:Interferon-gamma
keywords: Biomimetic; CD8; Protein nanoparticle; T cells; Tumor-associated antigen; Vaccine