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Nanoparticle Delivery Systems in Cancer Vaccines

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ABSTRACT

Therapeutic strategies that involve the manipulation of the host’s immune system are gaining momentum in cancer research. Antigen-loaded nanocarriers are capable of being actively taken up by antigen-presenting cells (APCs) and have shown promising potential in cancer immunotherapy by initiating a strong immunostimulatory cascade that results in potent antigen-specific immune responses against the cancer. Such carrier systems offer versatility in that they can simultaneously co-deliver adjuvants with the antigens to enhance APC activation and maturation. Furthermore, modifying the surface properties of these nanocarriers affords active targeting properties to APCs and/or enhanced accumulation in solid tumors. Here, we review some recent advances in these colloidal and particulate nanoscale systems designed for cancer immunotherapy and the potential for these systems to translate into clinical cancer vaccines.

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REFERENCES

  1. Cancer Facts & Figures 2009, American Cancer Society, Atlanta, 2009.

  2. Krishnamachari Y, Salem AK. Innovative strategies for co-delivering antigens and CpG oligonucleotides. Adv Drug Deliv Rev. 2009;61:205–17.

    CAS  PubMed  Google Scholar 

  3. Goforth R, Salem AK, Zhu XY, Miles S, Zhang XQ, Lee JH, et al. Immune stimulatory antigen loaded particles combined with depletion of regulatory T-cells induce potent tumor specific immunity in a mouse model of melanoma. Cancer Immunol Immunother. 2009;58:517–30.

    CAS  PubMed  Google Scholar 

  4. Blattman JN, Greenberg PD. Cancer immunotherapy: a treatment for the masses. Science. 2004;305:200–5.

    CAS  PubMed  Google Scholar 

  5. Diebold SS, Kaisho T, Hemmi H, Akira S, Sousa CRE. Innate antiviral responses by means of TLR7-mediated recognition of single-stranded RNA. Science. 2004;303:1529–31.

    CAS  PubMed  Google Scholar 

  6. Melief CJM. Cancer—immune pact with the enemy. Nature. 2007;450:803–4.

    CAS  PubMed  Google Scholar 

  7. Steinman RM, Banchereau J. Taking dendritic cells into medicine. Nature. 2007;449:419–26.

    CAS  PubMed  Google Scholar 

  8. Williams N. An immune boost to the war on cancer. Science. 1996;272:28–30.

    CAS  PubMed  Google Scholar 

  9. Sakhalkar HS, Dalal MK, Salem AK, Ansari R, Fu A, Kiani MF, et al. Leukocyte-inspired biodegradable particles that selectively and avidly adhere to inflamed endothelium in vitro and in vivo. Proc Natl Acad Sci USA. 2003;100:15895–900.

    CAS  PubMed  Google Scholar 

  10. Salem AK, Searson PC, Leong KW. Multifunctional nanorods for gene delivery. Nat Mater. 2003;2:668–71.

    CAS  PubMed  Google Scholar 

  11. Salem AK, Hung CF, Kim TW, Wu TC, Searson PC, Leong KW. Multi-component nanorods for vaccination applications. Nanotechnology. 2005;16:484–7.

    CAS  Google Scholar 

  12. Pearce ME, Melanko JB, Salem AK. Multifunctional nanorods for biomedical applications. Pharm Res. 2007;24:2335–52.

    CAS  PubMed  Google Scholar 

  13. Intra J, Salem AK. Characterization of the transgene expression generated by branched and linear polyethylenimine-plasmid DNA nanoparticles in vitro and after intraperitoneal injection in vivo. J Control Release. 2008;130:129–38.

    CAS  PubMed  Google Scholar 

  14. Pearce ME, Mai HQ, Lee N, Larsen SC, Salem AK. Silicalite nanoparticles that promote transgene expression. Nanotechnology. 19:(2008).

  15. Finn OJ. Human tumor antigens, immunosurveillance, and cancer vaccines. Immunol Res. 2006;36:73–82.

    CAS  PubMed  Google Scholar 

  16. Ochsenbein AF. Principles of tumor immunosurveillance and implications for immunotherapy. Cancer Gene Ther. 2002;9:1043–55.

    CAS  PubMed  Google Scholar 

  17. Zhang XQ, Dahle CE, Weiner GJ, Salem AK. A comparative study of the antigen-specific immune response induced by co-delivery of CpG ODN and antigen using fusion molecules or biodegradable microparticles. J Pharm Sci. 2007;96:3283–92.

    CAS  PubMed  Google Scholar 

  18. Torchilin VP. Multifunctional nanocarriers. Adv Drug Deliv Rev. 2006;58:1532–55.

    CAS  PubMed  Google Scholar 

  19. Torchilin VP. Micellar nanocarriers: pharmaceutical perspectives. Pharm Res. 2007;24:1–16.

    CAS  PubMed  Google Scholar 

  20. Torchilin VP. Nanocarriers. Pharm Res. 2007;24:2333–4.

    CAS  PubMed  Google Scholar 

  21. Torchilin VP. Multifunctional nanocarriers for delivery of drugs, genes, and diagnosticals in the body. FEBS J. 2009;276:85.

    Google Scholar 

  22. Couvreur P, Vauthier C. Nanotechnology: Intelligent design to treat complex disease. Pharm Res. 2006;23:1417–50.

    CAS  PubMed  Google Scholar 

  23. Hartig SM, Greene RR, Dikov MM, Prokop A, Davidson JM. Multifunctional nanoparticulate polyelectrolyte complexes. Pharm Res. 2007;24:2353–69.

    CAS  PubMed  Google Scholar 

  24. Staples M, Daniel K, Cima MJ, Langer R. Application of micro- and nano-electromechanical devices to drug delivery. Pharm Res. 2006;23:847–63.

    CAS  PubMed  Google Scholar 

  25. Sutton D, Nasongkla N, Blanco E, Gao JM. Functionalized micellar systems for cancer targeted drug delivery. Pharm Res. 2007;24:1029–46.

    CAS  PubMed  Google Scholar 

  26. van Vlerken LE, Vyas TK, Amiji MM. Poly(ethylene glycol)-modified nanocarriers for tumor-targeted and intracellular delivery. Pharm Res. 2007;24:1405–14.

    PubMed  Google Scholar 

  27. Zhang SF, Uludag H. Nanoparticulate systems for growth factor delivery. Pharm Res. 2009;26:1561–80.

    CAS  PubMed  Google Scholar 

  28. Ganta S, Devalapally H, Shahiwala A, Amiji M. A review of stimuli-responsive nanocarriers for drug and gene delivery. J Control Release. 2008;126:187–204.

    CAS  PubMed  Google Scholar 

  29. Jabr-Milane L, van Vlerken L, Devalapally H, Shenoy D, Komareddy S, Bhavsar M, et al. Multi-functional nanocarriers for targeted delivery of drugs and genes. J Control Release. 2008;130:121–8.

    CAS  PubMed  Google Scholar 

  30. Zhang XQ, Dahle CE, Baman NK, Rich N, Weiner GJ, Salem AK. Potent antigen-specific immune responses stimulated by codelivery of CpG ODN and antigens in degradable microparticles. J Immunother. 2007;30:469–78.

    PubMed  Google Scholar 

  31. Intra J, Salem AK. Fabrication, characterization and in vitro evaluation of Poly(D, L-Lactide-co-Glycolide) microparticles loaded with polyamidoamine-plasmid DNA dendriplexes for applications in nonviral gene delivery. J Pharm Sci. 2010;99:368–84.

    CAS  PubMed  Google Scholar 

  32. Zhang XQ, Intra J, Salem AK. Comparative study of poly (lactic-co-glycolic acid)-poly ethyleneimine-plasmid DNA microparticles prepared using double emulsion methods. J Microencapsul. 2008;25:1–12.

    PubMed  Google Scholar 

  33. Abbas AO, Donovan MD, Salem AK. Formulating poly(lactide-co-glycolide) particles for plasmid DNA delivery. J Pharm Sci. 2008;97:2448–61.

    CAS  PubMed  Google Scholar 

  34. Zhang XQ, Intra J, Salem AK. Conjugation of polyamidoamine dendrimers on biodegradable microparticles for nonviral gene delivery. Bioconjug Chem. 2007;18:2068–76.

    CAS  PubMed  Google Scholar 

  35. Alper J. Drug delivery—breaching the membrane. Science. 2002;296:838–9.

    CAS  PubMed  Google Scholar 

  36. Langer R. Drug delivery and targeting. Nature. 1998;392:5–10.

    CAS  PubMed  Google Scholar 

  37. Lasic DD. Doxorubicin in sterically stabilized liposomes. Nature. 1996;380:561–2.

    CAS  PubMed  Google Scholar 

  38. Szoka F. Molecular biology—The art of assembly. Science. 2008;319:578–9.

    CAS  PubMed  Google Scholar 

  39. Nii T, Ishii F. Encapsulation efficiency of water-soluble and insoluble drugs in liposomes prepared by the microencapsulation vesicle method. Int J Pharm. 2005;298:198–205.

    CAS  PubMed  Google Scholar 

  40. Karande P, Mitragotri S. Transcutaneous immunization: an overview of advantages, disease targets, vaccines, and delivery technologies. Annu Rev Chem Biomol Eng. 2010;1:175–201.

    CAS  Google Scholar 

  41. Frank MM. The reticuloendothelial system and bloodstream clearance. J Lab Clin Med. 1993;122:487–8.

    CAS  PubMed  Google Scholar 

  42. Worth LL, Jia SF, An T, Kleinerman ES. ImmTher, a lipophilic disaccharide derivative of muramyl dipeptide, up-regulates specific monocyte cytokine genes and activates monocyte-mediated tumoricidal activity. Cancer Immunol Immunother. 1999;48:312–20.

    CAS  PubMed  Google Scholar 

  43. Sangha R, North S. L-BLP25: a MUC1-targeted peptide vaccine therapy in prostate cancer. Expert Opin Biol Ther. 2007;7:1723–30.

    CAS  PubMed  Google Scholar 

  44. Vlad AM, Kettel JC, Alajez NM, Carlos CA, Finn OJ. MUC1 immunobiology: from discovery to clinical applications. Adv Immunol. 2004;82:249–93.

    CAS  PubMed  Google Scholar 

  45. Tapping RI, Akashi S, Miyake K, Godowski PJ, Tobias PS. Toll-like receptor 4, but not toll-like receptor 2, is a signaling receptor for Escherichia and Salmonella lipopolysaccharides. J Immunol. 2000;165:5780–7.

    CAS  PubMed  Google Scholar 

  46. De Becker G, Moulin V, Pajak B, Bruck C, Francotte M, Thiriart C, et al. The adjuvant monophosphoryl lipid A increases the function of antigen-presenting cells. Int Immunol. 2000;12:807–15.

    PubMed  Google Scholar 

  47. Agrawal B, Krantz MJ, Reddish MA, Longenecker BM. Rapid induction of primary human CD4+ and CD8+ T cell responses against cancer-associated MUC1 peptide epitopes. Int Immunol. 1998;10:1907–16.

    CAS  PubMed  Google Scholar 

  48. Sangha R, Butts C. L-BLP25: a peptide vaccine strategy in non small cell lung cancer. Clin Cancer Res. 2007;13:s4652–4.

    PubMed  Google Scholar 

  49. Chikh G, Schutze-Redelmeier MP. Liposomal delivery of CTL epitopes to dendritic cells. Biosci Rep. 2002;22:339–53.

    CAS  PubMed  Google Scholar 

  50. Ignatius R, Mahnke K, Rivera M, Hong K, Isdell F, Steinman RM, et al. Presentation of proteins encapsulated in sterically stabilized liposomes by dendritic cells initiates CD8(+) T-cell responses in vivo. Blood. 2000;96:3505–13.

    CAS  PubMed  Google Scholar 

  51. Faham A, Bennett D, Altin JG. Liposomal Ag engrafted with peptides of sequence derived from HMGB1 induce potent Ag-specific and anti-tumour immunity. Vaccine. 2009;27:5846–54.

    CAS  PubMed  Google Scholar 

  52. van Broekhoven CL, Parish CR, Demangel C, Britton WJ, Altin JG. Targeting dendritic cells with antigen-containing liposomes: a highly effective procedure for induction of antitumor immunity and for tumor immunotherapy. Cancer Res. 2004;64:4357–65.

    PubMed  Google Scholar 

  53. Li S, Rizzo MA, Bhattacharya S, Huang L. Characterization of cationic lipid-protamine-DNA (LPD) complexes for intravenous gene delivery. Gene Ther. 1998;5:930–7.

    CAS  PubMed  Google Scholar 

  54. Lv H, Zhang S, Wang B, Cui S, Yan J. Toxicity of cationic lipids and cationic polymers in gene delivery. J Control Release. 2006;114:100–9.

    CAS  PubMed  Google Scholar 

  55. Sakurai F, Terada T, Yasuda K, Yamashita F, Takakura Y, Hashida M. The role of tissue macrophages in the induction of proinflammatory cytokine production following intravenous injection of lipoplexes. Gene Ther. 2002;9:1120–6.

    CAS  PubMed  Google Scholar 

  56. Rudginsky S, Siders W, Ingram L, Marshall J, Scheule R, Kaplan J. Antitumor activity of cationic lipid complexed with immunostimulatory DNA. Mol Ther. 2001;4:347–55.

    CAS  PubMed  Google Scholar 

  57. Gursel I, Gursel M, Ishii KJ, Klinman DM. Sterically stabilized cationic liposomes improve the uptake and immunostimulatory activity of CpG oligonucleotides. J Immunol. 2001;167:3324–8.

    CAS  PubMed  Google Scholar 

  58. de Jong S, Chikh G, Sekirov L, Raney S, Semple S, Klimuk S, et al. Encapsulation in liposomal nanoparticles enhances the immunostimulatory, adjuvant and anti-tumor activity of subcutaneously administered CpG ODN. Cancer Immunol Immunother. 2007;56:1251–64.

    PubMed  Google Scholar 

  59. Gonzalez R, Hutchins L, Nemunaitis J, Atkins M, Schwarzenberger PO. Phase 2 trial of Allovectin-7 in advanced metastatic melanoma. Melanoma Res. 2006;16:521–6.

    CAS  PubMed  Google Scholar 

  60. Bedikian AY, Del Vecchio M. Allovectin-7 therapy in metastatic melanoma. Expert Opin Biol Ther. 2008;8:839–44.

    CAS  PubMed  Google Scholar 

  61. Krishnan L, Sprott GD. Archaeosome adjuvants: immunological capabilities and mechanism(s) of action. Vaccine. 2008;26:2043–55.

    CAS  PubMed  Google Scholar 

  62. Bligh EG, Dyer WJ. A rapid method of total lipid extraction and purification. Can J Biochem Physiol. 1959;37:911–7.

    CAS  PubMed  Google Scholar 

  63. Omri A, Makabi-Panzu B, Agnew BJ, Sprott GD, Patel GB. Influence of coenzyme Q10 on tissue distribution of archaeosomes, and pegylated archaeosomes, administered to mice by oral and intravenous routes. J Drug Target. 2000;7:383–92.

    CAS  PubMed  Google Scholar 

  64. Krishnan L, Dennis Sprott G. Archaeosomes as self-adjuvanting delivery systems for cancer vaccines. J Drug Target. 2003;11:515–24.

    CAS  PubMed  Google Scholar 

  65. Krishnan L, Sad S, Patel GB, Sprott GD. Archaeosomes induce enhanced cytotoxic T lymphocyte responses to entrapped soluble protein in the absence of interleukin 12 and protect against tumor challenge. Cancer Res. 2003;63:2526–34.

    CAS  PubMed  Google Scholar 

  66. Krishnan L, Sad S, Patel GB, Sprott GD. Archaeosomes induce long-term CD8+ cytotoxic T cell response to entrapped soluble protein by the exogenous cytosolic pathway, in the absence of CD4+ T cell help. J Immunol. 2000;165:5177–85.

    CAS  PubMed  Google Scholar 

  67. Sprott GD, Dicaire CJ, Cote JP, Whitfield DM. Adjuvant potential of archaeal synthetic glycolipid mimetics critically depends on the glyco head group structure. Glycobiology. 2008;18:559–65.

    CAS  PubMed  Google Scholar 

  68. Patel GB, Omri A, Deschatelets L, Sprott GD. Safety of archaeosome adjuvants evaluated in a mouse model. J Liposome Res. 2002;12:353–72.

    CAS  PubMed  Google Scholar 

  69. Reddy R, Zhou F, Huang L, Carbone F, Bevan M, Rouse BT. pH sensitive liposomes provide an efficient means of sensitizing target cells to class I restricted CTL recognition of a soluble protein. J Immunol Meth. 1991;141:157–63.

    CAS  Google Scholar 

  70. Harding CV, Collins DS, Slot JW, Geuze HJ, Unanue ER. Liposome-encapsulated antigens are processed in lysosomes, recycled, and presented to T cells. Cell. 1991;64:393–401.

    CAS  PubMed  Google Scholar 

  71. Alving CR, Koulchin V, Glenn GM, Rao M. Liposomes as carriers of peptide antigens: induction of antibodies and cytotoxic T lymphocytes to conjugated and unconjugated peptides. Immunol Rev. 1995;145:5–31.

    CAS  PubMed  Google Scholar 

  72. Nakanishi M, Uchida T, Sugawa H, Ishiura M, Okada Y. Efficient introduction of contents of liposomes into cells using HVJ (Sendai virus). Exp Cell Res. 1985;159:399–409.

    CAS  PubMed  Google Scholar 

  73. Mizuguchi H, Nakanishi M, Nakanishi T, Nakagawa T, Nakagawa S, Mayumi T. Application of fusogenic liposomes containing fragment A of diphtheria toxin to cancer therapy. Br J Cancer. 1996;73:472–6.

    CAS  PubMed  Google Scholar 

  74. Nakanishi M, Mizuguchia H, Ashihara K, Senda T, Akuta T, Okabe J, et al. Gene transfer vectors based on Sendai virus. J Control Release. 1998;54:61–8.

    CAS  PubMed  Google Scholar 

  75. Yoshikawa T, Okada N, Tsujino M, Gao JQ, Hayashi A, Tsutsumi Y, et al. Vaccine efficacy of fusogenic liposomes containing tumor cell-lysate against murine B16BL6 melanoma. Biol Pharm Bull. 2006;29:100–4.

    CAS  PubMed  Google Scholar 

  76. Plotkin SL, Plotkin SA. A short history of vaccines. In: Plotkin S, Orenstein W, editors. vaccines. Philadelphia: WB Saunders Company; 2004. p. 1–15.

    Google Scholar 

  77. Speiser DE, Miranda R, Zakarian A, Bachmann MF, McKall-Faienza K, Odermatt B, et al. Self antigens expressed by solid tumors Do not efficiently stimulate naive or activated T cells: implications for immunotherapy. J Exp Med. 1997;186:645–53.

    CAS  PubMed  Google Scholar 

  78. Arlen PM, Pazdur M, Skarupa L, Rauckhorst M, Gulley JL. A randomized phase II study of docetaxel alone or in combination with PANVAC-V (vaccinia) and PANVAC-F (fowlpox) in patients with metastatic breast cancer (NCI 05-C-0229). Clin Breast Cancer. 2006;7:176–9.

    CAS  PubMed  Google Scholar 

  79. Gulley JL, Arlen PM, Madan RA, Tsang KY, Pazdur MP, Skarupa L, et al. Immunologic and prognostic factors associated with overall survival employing a poxviral-based PSA vaccine in metastatic castrate-resistant prostate cancer. Cancer Immunol Immunother. (2009).

  80. Amato RJ. 5T4-modified vaccinia Ankara: progress in tumor-associated antigen-based immunotherapy. Expert Opin Biol Ther. 2010;10:281–7.

    CAS  PubMed  Google Scholar 

  81. Harrop R, Ryan MG, Myers KA, Redchenko I, Kingsman SM, Carroll MW. Active treatment of murine tumors with a highly attenuated vaccinia virus expressing the tumor associated antigen 5 T4 (TroVax) is CD4+ T cell dependent and antibody mediated. Cancer Immunol Immunother. 2006;55:1081–90.

    CAS  PubMed  Google Scholar 

  82. Huang X, Yang Y. Innate immune recognition of viruses and viral vectors. Hum Gene Ther. 2009;20:293–301.

    CAS  PubMed  Google Scholar 

  83. Peruzzi D, Dharmapuri S, Cirillo A, Bruni BE, Nicosia A, Cortese R, et al. A novel chimpanzee serotype-based adenoviral vector as delivery tool for cancer vaccines. Vaccine. 2009;27:1293–300.

    CAS  PubMed  Google Scholar 

  84. Ludwig C, Wagner R. Virus-like particles-universal molecular toolboxes. Curr Opin Biotechnol. 2007;18:537–45.

    CAS  PubMed  Google Scholar 

  85. Deml L, Speth C, Dierich MP, Wolf H, Wagner R. Recombinant HIV-1 Pr55gag virus-like particles: potent stimulators of innate and acquired immune responses. Mol Immunol. 2005;42:259–77.

    CAS  PubMed  Google Scholar 

  86. Marsac D, Loirat D, Petit C, Schwartz O, Michel ML. Enhanced presentation of major histocompatibility complex class I-restricted human immunodeficiency virus type 1 (HIV-1) Gag-specific epitopes after DNA immunization with vectors coding for vesicular stomatitis virus glycoprotein-pseudotyped HIV-1 Gag particles. J Virol. 2002;76:7544–53.

    CAS  PubMed  Google Scholar 

  87. Villa LL, Costa RL, Petta CA, Andrade RP, Ault KA, Giuliano AR, et al. Prophylactic quadrivalent human papillomavirus (types 6, 11, 16, and 18) L1 virus-like particle vaccine in young women: a randomised double-blind placebo-controlled multicentre phase II efficacy trial. Lancet Oncol. 2005;6:271–8.

    PubMed  Google Scholar 

  88. Garland SM, Hernandez-Avila M, Wheeler CM, Perez G, Harper DM, Leodolter S, et al. Quadrivalent vaccine against human papillomavirus to prevent anogenital diseases. N Engl J Med. 2007;356:1928–43.

    CAS  PubMed  Google Scholar 

  89. Adamina M, Guller U, Bracci L, Heberer M, Spagnoli GC, Schumacher R. Clinical applications of virosomes in cancer immunotherapy. Expert Opin Biol Ther. 2006;6:1113–21.

    CAS  PubMed  Google Scholar 

  90. Zurbriggen R. Immunostimulating reconstituted influenza virosomes. Vaccine. 2003;21:921–4.

    CAS  PubMed  Google Scholar 

  91. Schumacher R, Adamina M, Zurbriggen R, Bolli M, Padovan E, Zajac P, et al. Influenza virosomes enhance class I restricted CTL induction through CD4+ T cell activation. Vaccine. 2004;22:714–23.

    CAS  PubMed  Google Scholar 

  92. Wiedermann U, Wiltschke C, Jasinska J, Kundi M, Zurbriggen R, Garner-Spitzer E, et al. A virosomal formulated Her-2/neu multi-peptide vaccine induces Her-2/neu-specific immune responses in patients with metastatic breast cancer: a phase I study. Breast Cancer Res Treat. 2010;119:673–83.

    CAS  PubMed  Google Scholar 

  93. Amacker M, Engler O, Kammer AR, Vadrucci S, Oberholzer D, Cerny A, et al. Peptide-loaded chimeric influenza virosomes for efficient in vivo induction of cytotoxic T cells. Int Immunol. 2005;17:695–704.

    CAS  PubMed  Google Scholar 

  94. Schumacher R, Amacker M, Neuhaus D, Rosenthal R, Groeper C, Heberer M, et al. Efficient induction of tumoricidal cytotoxic T lymphocytes by HLA-A0201 restricted, melanoma associated, L(27)Melan-A/MART-1(26-35) peptide encapsulated into virosomes in vitro. Vaccine. 2005;23:5572–82.

    CAS  PubMed  Google Scholar 

  95. Li Q, Gao JQ, Qiu LY, Cui FD, Jin Y. Enhanced immune responses induced by vaccine using Sendai virosomes as carrier. Int J Pharm. 2007;329:117–21.

    CAS  PubMed  Google Scholar 

  96. Gupta RK, Chang AC, Siber GR. Biodegradable polymer microspheres as vaccine adjuvants and delivery systems. Modulation Immune Response Vaccine Antigens. 1998;92:63–78.

    CAS  Google Scholar 

  97. Hedley ML, Curley J, Urban R. Microspheres containing plasmid-encoded antigens elicit cytotoxic T-cell responses. Nat Med. 1998;4:365–8.

    CAS  PubMed  Google Scholar 

  98. Helson R, Olszewska W, Singh M, Megede JZ, Melero JA, Hagan DO, et al. Polylactide-co-glycolide (PLG) microparticles modify the immune response to DNA vaccination. Vaccine. 2008;26:753–61.

    CAS  PubMed  Google Scholar 

  99. Lassalle V, Ferreira ML. PLA nano- and microparticles for drug delivery: An overview of the methods of preparation. Macromol Biosci. 2007;7:767–83.

    CAS  PubMed  Google Scholar 

  100. Krishnamachari Y, Madan P, Lin SS. Development of pH- and time-dependent oral microparticles to optimize budesonide delivery to ileum and colon. Int J Pharm. 2007;338:238–47.

    CAS  PubMed  Google Scholar 

  101. Kumar PS, Ramakrishna S, Saini TR, Diwan PV. Influence of microencapsulation method and peptide loading on formulation of poly(lactide-co-glycolide) insulin nanoparticles. Pharmazie. 2006;61:613–7.

    CAS  PubMed  Google Scholar 

  102. Mundargi RC, Babu VR, Rangaswamy V, Patel P, Aminabhavi TM. Nano/micro technologies for delivering macromolecular therapeutics using poly(D, L-lactide-co-glycolide) and its derivatives. J Control Release. 2008;125:193–209.

    CAS  PubMed  Google Scholar 

  103. Pean JM, Venier-Julienne MC, Boury F, Menei P, Denizot B, Benoit JP. NGF release from poly(D, L-lactide-co-glycolide) microspheres. Effect of some formulation parameters on encapsulated NGF stability. J Control Release. 1998;56:175–87.

    CAS  PubMed  Google Scholar 

  104. Raghuvanshi RS, Katare YK, Lalwani K, Ali MM, Singh O, Panda AK. Improved immune response from biodegradable polymer particles entrapping tetanus toxoid by use of different immunization protocol and adjuvants. Int J Pharm. 2002;245:109–21.

    CAS  PubMed  Google Scholar 

  105. Román BS, Irache JM, Gómez S, Tsapis N, Gamazo C, Espuelas MS. Co-encapsulation of an antigen and CpG oligonucleotides into PLGA microparticles by TROMS technology. Eur J Pharm Biopharm. 2008;70:98–108.

    Google Scholar 

  106. Singh M, O’Hagan DT. Recent advances in vaccine adjuvants. Pharm Res. 2002;19:715–28.

    CAS  PubMed  Google Scholar 

  107. Kovacsovics-Bankowski M, Rock KL. A phagosome-to-cytosol pathway for exogenous antigens presented on MHC class I molecules. Science. 1995;267:243–6.

    CAS  PubMed  Google Scholar 

  108. Waeckerle-Men Y, Groettrup M. PLGA microspheres for improved antigen delivery to dendritic cells as cellular vaccines. Adv Drug Deliv Rev. 2005;57:475–82.

    CAS  PubMed  Google Scholar 

  109. Nikou KN, Stivaktakis N, Avgoustakis K, Sotiropoulou PA, Perez SA, Baxevanis CN, et al. A HER-2/neu peptide admixed with PLA microspheres induces a Th1-biased immune response in mice. Biochim Biophys Acta. 2005;1725:182–9.

    CAS  PubMed  Google Scholar 

  110. Men Y, Audran R, Thomasin C, Eberl G, Demotz S, Merkle HP, et al. MHC class I- and class II-restricted processing and presentation of microencapsulated antigens. Vaccine. 1999;17:1047–56.

    CAS  PubMed  Google Scholar 

  111. O’Hagan DT, Jeffery H, Davis SS. Long-term antibody responses in mice following subcutaneous immunization with ovalbumin entrapped in biodegradable microparticles. Vaccine. 1993;11:965–9.

    PubMed  Google Scholar 

  112. Uchida T, Martin S, Foster TP, Wardley RC, Grimm S. Dose and load studies for subcutaneous and oral delivery of poly(lactide-co-glycolide) microspheres containing ovalbumin. Pharm Res. 1994;11:1009–15.

    CAS  PubMed  Google Scholar 

  113. Igartua M, Hernandez RM, Esquisabel A, Gascon AR, Calvo MB, Pedraz JL. Enhanced immune response after subcutaneous and oral immunization with biodegradable PLGA microspheres. J Control Release. 1998;56:63–73.

    CAS  PubMed  Google Scholar 

  114. Zhang XQ, Dahle CE, Baman NK, Rich N, Weiner GJ, Salem AK. Potent antigen-specific immune responses stimulated by codelivery of CpG ODN and antigens in degradable microparticles. J Immunother. 2007;30:469–78.

    PubMed  Google Scholar 

  115. Elamanchili P, Lutsiak CM, Hamdy S, Diwan M, Samuel J. “Pathogen-mimicking” nanoparticles for vaccine delivery to dendritic cells. J Immunother. 2007;30:378–95.

    CAS  PubMed  Google Scholar 

  116. Goforth R, Salem AK, Zhu X, Miles S, Zhang XQ, Lee JH, et al. Immune stimulatory antigen loaded particles combined with depletion of regulatory T-cells induce potent tumor specific immunity in a mouse model of melanoma. Cancer Immunol Immunother. 2009;58:517–30.

    CAS  PubMed  Google Scholar 

  117. Hamdy S, Molavi O, Ma Z, Haddadi A, Alshamsan A, Gobti Z, et al. Co-delivery of cancer-associated antigen and Toll-like receptor 4 ligand in PLGA nanoparticles induces potent CD8+ T cell-mediated anti-tumor immunity. Vaccine. 2008;26:5046–57.

    CAS  PubMed  Google Scholar 

  118. Mattheolabakis G, Lagoumintzis G, Panagi Z, Papadimitriou E, Partidos CD, Avgoustakis K. Transcutaneous delivery of a nanoencapsulated antigen: induction of immune responses. Int J Pharm. 2010;385:187–93.

    CAS  PubMed  Google Scholar 

  119. Dominguez AL, Lustgarten J. Targeting the tumor microenvironment with anti-neu/anti-CD40 conjugated nanoparticles for the induction of antitumor immune responses. Vaccine. 2010;28:1383–90.

    CAS  PubMed  Google Scholar 

  120. O’Hagan DT, Singh M, Ulmer JB. Microparticle-based technologies for vaccines. Methods. 2006;40:10–9.

    PubMed  Google Scholar 

  121. Johansen P, Martinez Gomez JM, Gander B. Development of synthetic biodegradable microparticulate vaccines: a roller coaster story. Expert Rev Vaccines. 2007;6:471–4.

    CAS  PubMed  Google Scholar 

  122. Standley SM, Kwon YJ, Murthy N, Kunisawa J, Shastri N, Guillaudeu SJ, et al. Acid-degradable particles for protein-based vaccines: enhanced survival rate for tumor-challenged mice using ovalbumin model. Bioconjug Chem. 2004;15:1281–8.

    CAS  PubMed  Google Scholar 

  123. Cohen JA, Beaudette TT, Tseng WW, Bachelder EM, Mende I, Engleman EG, et al. T-cell activation by antigen-loaded pH-sensitive hydrogel particles in vivo: the effect of particle size. Bioconjug Chem. 2009;20:111–9.

    CAS  PubMed  Google Scholar 

  124. Beaudette TT, Bachelder EM, Cohen JA, Obermeyer AC, Broaders KE, Frechet JM, et al. in vivo studies on the effect of co-encapsulation of CpG DNA and antigen in acid-degradable microparticle vaccines. Mol Pharm. 2009;6:1160–9.

    CAS  PubMed  Google Scholar 

  125. Facts & Statistics, 2009, American Brain Tumor Association, Des Plaines, IL, 2009.

  126. Fakhrai H, Dorigo O, Shawler DL, Lin H, Mercola D, Black KL, et al. Eradication of established intracranial rat gliomas by transforming growth factor beta antisense gene therapy. Proc Natl Acad Sci USA. 1996;93:2909–14.

    CAS  PubMed  Google Scholar 

  127. Maggard M, Meng L, Ke B, Allen R, Devgan L, Imagawa DK. Antisense TGF-beta2 immunotherapy for hepatocellular carcinoma: treatment in a rat tumor model. Ann Surg Oncol. 2001;8:32–7.

    CAS  PubMed  Google Scholar 

  128. Schlingensiepen KH, Schlingensiepen R, Steinbrecher A, Hau P, Bogdahn U, Fischer-Blass B, et al. Targeted tumor therapy with the TGF-beta 2 antisense compound AP 12009. Cytokine Growth Factor Rev. 2006;17:129–39.

    CAS  PubMed  Google Scholar 

  129. Liu Y, Wang Q, Kleinschmidt-DeMasters BK, Franzusoff A, Ng KY, Lillehei KO. TGF-beta2 inhibition augments the effect of tumor vaccine and improves the survival of animals with pre-established brain tumors. J Neurooncol. 2007;81:149–62.

    CAS  PubMed  Google Scholar 

  130. Kreuter J. Nanoparticulate systems for brain delivery of drugs. Adv Drug Deliv Rev. 2001;47:65–81.

    CAS  PubMed  Google Scholar 

  131. Lockman PR, Mumper RJ, Khan MA, Allen DD. Nanoparticle technology for drug delivery across the blood-brain barrier. Drug Dev Ind Pharm. 2002;28:1–13.

    CAS  PubMed  Google Scholar 

  132. Vauthier C, Dubernet C, Fattal E, Pinto-Alphandary H, Couvreur P. Poly(alkylcyanoacrylates) as biodegradable materials for biomedical applications. Adv Drug Deliv Rev. 2003;55:519–48.

    CAS  PubMed  Google Scholar 

  133. Yang SC, Ge HX, Hu Y, Jiang XQ, Yang CZ. Doxorubicin-loaded poly(butylcyanoacrylate) nanoparticles produced by emulsifier-free emulsion polymerization. J Appl Polym Sci. 2000;78:517–26.

    CAS  Google Scholar 

  134. Soma CE, Dubernet C, Bentolila D, Benita S, Couvreur P. Reversion of multidrug resistance by co-encapsulation of doxorubicin and cyclosporin A in polyalkylcyanoacrylate nanoparticles. Biomaterials. 2000;21:1–7.

    CAS  PubMed  Google Scholar 

  135. Soma CE, Dubernet C, Barratt G, Nemati F, Appel M, Benita S, et al. Ability of doxorubicin-loaded nanoparticles to overcome multidrug resistance of tumor cells after their capture by macrophages. Pharm Res. 1999;16:1710–6.

    CAS  PubMed  Google Scholar 

  136. Schneider T, Becker A, Ringe K, Reinhold A, Firsching R, Sabel BA. Brain tumor therapy by combined vaccination and antisense oligonucleotide delivery with nanoparticles. J Neuroimmunol. 2008;195:21–7.

    CAS  PubMed  Google Scholar 

  137. Alyautdin RN, Tezikov EB, Ramge P, Kharkevich DA, Begley DJ, Kreuter J. Significant entry of tubocurarine into the brain of rats by adsorption to polysorbate 80-coated polybutylcyanoacrylate nanoparticles: an in situ brain perfusion study. J Microencapsul. 1998;15:67–74.

    CAS  PubMed  Google Scholar 

  138. Kreuter J, Alyautdin RN, Kharkevich DA, Ivanov AA. Passage of peptides through the blood-brain barrier with colloidal polymer particles (nanoparticles). Brain Res. 1995;674:171–4.

    CAS  PubMed  Google Scholar 

  139. Schroder U, Sabel BA. Nanoparticles, a drug carrier system to pass the blood-brain barrier, permit central analgesic effects of i.v. dalargin injections. Brain Res. 1996;710:121–4.

    CAS  PubMed  Google Scholar 

  140. Kreuter J, Petrov VE, Kharkevich DA, Alyautdin RN. Influence of the type of surfactant on the analgesic effects in duced by the peptide dalargin after its delivery across the blood-brain barrier using surfactant-coated nanoparticles. J Control Release. 1997;49:81–7.

    CAS  Google Scholar 

  141. Schroeder U, Sommerfeld P, Ulrich S, Sabel BA. Nanoparticle technology for delivery of drugs across the blood-brain barrier. J Pharm Sci. 1998;87:1305–7.

    CAS  PubMed  Google Scholar 

  142. Schroeder U, Sommerfeld P, Sabel BA. Efficacy of oral dalargin-loaded nanoparticle delivery across the blood-brain barrier. Peptides. 1998;19:777–80.

    CAS  PubMed  Google Scholar 

  143. Gulyaev AE, Gelperina SE, Skidan IN, Antropov AS, Kivman GY, Kreuter J. Significant transport of doxorubicin into the brain with polysorbate 80-coated nanoparticles. Pharm Res. 1999;16:1564–9.

    CAS  PubMed  Google Scholar 

  144. Schlingensiepen KH, Fischer-Blass B, Schmaus S, Ludwig S. Antisense therapeutics for tumor treatment: the TGF-beta2 inhibitor AP 12009 in clinical development against malignant tumors. Recent Results Cancer Res. 2008;177:137–50.

    CAS  PubMed  Google Scholar 

  145. Kaul G, Amiji M. Long-circulating poly(ethylene glycol)-modified gelatin nanoparticles for intracellular delivery. Pharm Res. 2002;19:1061–7.

    CAS  PubMed  Google Scholar 

  146. Kreuter J. Nanoparticulate systems in drug delivery and targeting. J Drug Target. 1995;3:171–3.

    CAS  PubMed  Google Scholar 

  147. Coester C, Nayyar P, Samuel J. In vitro uptake of gelatin nanoparticles by murine dendritic cells and their intracellular localisation. Eur J Pharm Biopharm. 2006;62:306–14.

    CAS  PubMed  Google Scholar 

  148. Bourquin C, Anz D, Zwiorek K, Lanz AL, Fuchs S, Weigel S, et al. Targeting CpG oligonucleotides to the lymph node by nanoparticles elicits efficient antitumoral immunity. J Immunol. 2008;181:2990–8.

    CAS  PubMed  Google Scholar 

  149. Makidon PE, Bielinska AU, Nigavekar SS, Janczak KW, Knowlton J, Scott AJ, et al. Pre-clinical evaluation of a novel nanoemulsion-based hepatitis B mucosal vaccine. PLoS ONE. 2008;3:e2954.

    PubMed  Google Scholar 

  150. Bielinska AU, Janczak KW, Landers JJ, Markovitz DM, Montefiori DC, Baker Jr JR. Nasal immunization with a recombinant HIV gp120 and nanoemulsion adjuvant produces Th1 polarized responses and neutralizing antibodies to primary HIV type 1 isolates. AIDS Res Hum Retroviruses. 2008;24:271–81.

    CAS  PubMed  Google Scholar 

  151. Huang MH, Huang CY, Lin SC, Chen JH, Ku CC, Chou AH, et al. Enhancement of potent antibody and T-cell responses by a single-dose, novel nanoemulsion-formulated pandemic influenza vaccine. Microbes Infect. 2009;11:654–60.

    CAS  PubMed  Google Scholar 

  152. Shi R, Hong L, Wu D, Ning X, Chen Y, Lin T, et al. Enhanced immune response to gastric cancer specific antigen Peptide by coencapsulation with CpG oligodeoxynucleotides in nanoemulsion. Cancer Biol Ther. 2005;4:218–24.

    CAS  PubMed  Google Scholar 

  153. Ge W, Sui YF, Wu DC, Sun YJ, Chen GS, Li ZS, et al. MAGE-1/Heat shock protein 70/MAGE-3 fusion protein vaccine in nanoemulsion enhances cellular and humoral immune responses to MAGE-1 or MAGE-3 in vivo. Cancer Immunol Immunother. 2006;55:841–9.

    PubMed  Google Scholar 

  154. Ge W, Sun YJ, Li Y, Zhang SH, Zhang XM, Huang Y, et al. Anti-tumor immune responses of nanoemulsion-encapsulated MHS vaccine. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2008;24:457–60.

    CAS  PubMed  Google Scholar 

  155. Ge W, Hu PZ, Huang Y, Wang XM, Zhang XM, Sun YJ, et al. The antitumor immune responses induced by nanoemulsion-encapsulated MAGE1-HSP70/SEA complex protein vaccine following different administration routes. Oncol Rep. 2009;22:915–20.

    CAS  PubMed  Google Scholar 

  156. Ge W, Li Y, Li ZS, Zhang SH, Sun YJ, Hu PZ, et al. The antitumor immune responses induced by nanoemulsion-encapsulated MAGE1-HSP70/SEA complex protein vaccine following peroral administration route. Cancer Immunol Immunother. 2009;58:201–8.

    CAS  PubMed  Google Scholar 

  157. Hang QL, Ding J, Gong AC, Yu ZC, Qiao TD, Chen BJ, et al. Screening of bioactive peptide that mimic the epitope of gastric cancer associated antigen. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2003;19:308–10.

    PubMed  Google Scholar 

  158. Xu L, Jin BQ, Fan DM. Selection and identification of mimic epitopes for gastric cancer-associated antigen MG7 Ag. Mol Cancer Ther. 2003;2:301–6.

    CAS  PubMed  Google Scholar 

  159. Akagi T, Kaneko T, Kida T, Akashi M. Preparation and characterization of biodegradable nanoparticles based on poly(gamma-glutamic acid) with l-phenylalanine as a protein carrier. J Control Release. 2005;108:226–36.

    CAS  PubMed  Google Scholar 

  160. Akagi T, Higashi M, Kaneko T, Kida T, Akashi M. In vitro enzymatic degradation of nanoparticles prepared from hydrophobically-modified poly(gamma-glutamic acid). Macromol Biosci. 2005;5:598–602.

    CAS  PubMed  Google Scholar 

  161. Yoshikawa T, Okada N, Oda A, Matsuo K, Mukai Y, Yoshioka Y, et al. Development of amphiphilic gamma-PGA-nanoparticle based tumor vaccine: potential of the nanoparticulate cytosolic protein delivery carrier. Biochem Biophys Res Commun. 2008;366:408–13.

    CAS  PubMed  Google Scholar 

  162. Uto T, Wang X, Sato K, Haraguchi M, Akagi T, Akashi M, et al. Targeting of antigen to dendritic cells with poly(gamma-glutamic acid) nanoparticles induces antigen-specific humoral and cellular immunity. J Immunol. 2007;178:2979–86.

    CAS  PubMed  Google Scholar 

  163. Matsuo K, Yoshikawa T, Oda A, Akagi T, Akashi M, Mukai Y, et al. Efficient generation of antigen-specific cellular immunity by vaccination with poly(gamma-glutamic acid) nanoparticles entrapping endoplasmic reticulum-targeted peptides. Biochem Biophys Res Commun. 2007;362:1069–72.

    CAS  PubMed  Google Scholar 

  164. Yoshikawa T, Okada N, Oda A, Matsuo K, Kayamuro H, Ishii Y, et al. Nanoparticles built by self-assembly of amphiphilic gamma-PGA can deliver antigens to antigen-presenting cells with high efficiency: a new tumor-vaccine carrier for eliciting effector T cells. Vaccine. 2008;26:1303–13.

    CAS  PubMed  Google Scholar 

  165. Yamaguchi S, Tatsumi T, Takehara T, Sasakawa A, Yamamoto M, Kohga K, et al. EphA2-derived peptide vaccine with amphiphilic poly(gamma-glutamic acid) nanoparticles elicits an anti-tumor effect against mouse liver tumor. Cancer Immunol Immunother 2009.

  166. Lowery AR, Gobin AM, Day ES, Halas NJ, West JL. Immunonanoshells for targeted photothermal ablation of tumor cells. Int J Nanomedicine. 2006;1:149–54.

    CAS  PubMed  Google Scholar 

  167. Bernardi RJ, Lowery AR, Thompson PA, Blaney SM, West JL. Immunonanoshells for targeted photothermal ablation in medulloblastoma and glioma: an in vitro evaluation using human cell lines. J Neurooncol. 2008;86:165–72.

    PubMed  Google Scholar 

  168. Ojeda R, de Paz JL, Barrientos AG, Martin-Lomas M, Penades S. Preparation of multifunctional glyconanoparticles as a platform for potential carbohydrate-based anticancer vaccines. Carbohydr Res. 2007;342:448–59.

    CAS  PubMed  Google Scholar 

  169. Day ES, Morton JG, West JL. Nanoparticles for thermal cancer therapy. J Biomech Eng. 2009;131:074001.

    PubMed  Google Scholar 

  170. Shinkai M, Yanase M, Honda H, Wakabayashi T, Yoshida J, Kobayashi T. Intracellular hyperthermia for cancer using magnetite cationic liposomes: in vitro study. Jpn J Cancer Res. 1996;87:1179–83.

    CAS  PubMed  Google Scholar 

  171. Yanase M, Shinkai M, Honda H, Wakabayashi T, Yoshida J, Kobayashi T. Intracellular hyperthermia for cancer using magnetite cationic liposomes: ex vivo study. Jpn J Cancer Res. 1997;88:630–2.

    CAS  PubMed  Google Scholar 

  172. Ito A, Tanaka K, Kondo K, Shinkai M, Honda H, Matsumoto K, et al. Tumor regression by combined immunotherapy and hyperthermia using magnetic nanoparticles in an experimental subcutaneous murine melanoma. Cancer Sci. 2003;94:308–13.

    CAS  PubMed  Google Scholar 

  173. Ito A, Tanaka K, Honda H, Abe S, Yamaguchi H, Kobayashi T. Complete regression of mouse mammary carcinoma with a size greater than 15 mm by frequent repeated hyperthermia using magnetite nanoparticles. J Biosci Bioeng. 2003;96:364–9.

    CAS  PubMed  Google Scholar 

  174. Ito A, Shinkai M, Honda H, Yoshikawa K, Saga S, Wakabayashi T, et al. Heat shock protein 70 expression induces antitumor immunity during intracellular hyperthermia using magnetite nanoparticles. Cancer Immunol Immunother. 2003;52:80–8.

    CAS  PubMed  Google Scholar 

  175. Ito A, Matsuoka F, Honda H, Kobayashi T. Heat shock protein 70 gene therapy combined with hyperthermia using magnetic nanoparticles. Cancer Gene Ther. 2003;10:918–25.

    CAS  PubMed  Google Scholar 

  176. Ito A, Matsuoka F, Honda H, Kobayashi T. Antitumor effects of combined therapy of recombinant heat shock protein 70 and hyperthermia using magnetic nanoparticles in an experimental subcutaneous murine melanoma. Cancer Immunol Immunother. 2004;53:26–32.

    CAS  PubMed  Google Scholar 

  177. Ito A, Kuga Y, Honda H, Kikkawa H, Horiuchi A, Watanabe Y, et al. Magnetite nanoparticle-loaded anti-HER2 immunoliposomes for combination of antibody therapy with hyperthermia. Cancer Lett. 2004;212:167–75.

    CAS  PubMed  Google Scholar 

  178. Tanaka K, Ito A, Kobayashi T, Kawamura T, Shimada S, Matsumoto K, et al. Heat immunotherapy using magnetic nanoparticles and dendritic cells for T-lymphoma. J Biosci Bioeng. 2005;100:112–5.

    CAS  PubMed  Google Scholar 

  179. Tanaka K, Ito A, Kobayashi T, Kawamura T, Shimada S, Matsumoto K, et al. Intratumoral injection of immature dendritic cells enhances antitumor effect of hyperthermia using magnetic nanoparticles. Int J Cancer. 2005;116:624–33.

    CAS  PubMed  Google Scholar 

  180. Ito A, Honda H, Kobayashi T. Cancer immunotherapy based on intracellular hyperthermia using magnetite nanoparticles: a novel concept of “heat-controlled necrosis” with heat shock protein expression. Cancer Immunol Immunother. 2006;55:320–8.

    CAS  PubMed  Google Scholar 

  181. Ito A, Kobayashi T, Honda H. Heat immunotherapy with heat shock protein expression by hyperthermia using magnetite nanoparticles. Ann Cancer Res Therap. 2007;15:27–34.

    Google Scholar 

  182. Takada T, Yamashita T, Sato M, Sato A, Ono I, Tamura Y, et al. Growth inhibition of re-challenge B16 melanoma transplant by conjugates of melanogenesis substrate and magnetite nanoparticles as the basis for developing melanoma-targeted chemo-thermo-immunotherapy. J Biomed Biotechnol. 2009;2009:457936.

    PubMed  Google Scholar 

  183. Kikumori T, Kobayashi T, Sawaki M, Imai T. Anti-cancer effect of hyperthermia on breast cancer by magnetite nanoparticle-loaded anti-HER2 immunoliposomes. Breast Cancer Res Treat. 2009;113:435–41.

    CAS  PubMed  Google Scholar 

  184. Jimbow K, Takada T, Sato M. Melanin biology and translational research strategy; melanogenesis and nanomedicine as the basis for melanoma-targeted DDS and chemothermo-immunotherapy. Pigment Cell Melanoma Res. 2008;21:243.

    Google Scholar 

  185. Dow SW, Fradkin LG, Liggitt DH, Willson AP, Heath TD, Potter TA. Lipid-DNA complexes induce potent activation of innate immune responses and antitumor activity when administered intravenously. J Immunol. 1999;163:1552–61.

    CAS  PubMed  Google Scholar 

  186. Dharmapuri S, Peruzzi D, Aurisicchio L. Engineered adenovirus serotypes for overcoming anti-vector immunity. Expert Opin Biol Ther. 2009;9:1279–87.

    CAS  PubMed  Google Scholar 

  187. Ramlau R, Quoix E, Rolski J, Pless M, Lena H, Levy E, et al. A phase II study of Tg4010 (Mva-Muc1-Il2) in association with chemotherapy in patients with stage III/IV Non-small cell lung cancer. J Thorac Oncol. 2008;3:735–44.

    PubMed  Google Scholar 

  188. Foged C, Sundblad A, Hovgaard L. Targeting vaccines to dendritic cells. Pharm Res. 2002;19:229–38.

    CAS  PubMed  Google Scholar 

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ACKNOWLEDGEMENTS

We gratefully acknowledge support from the American Cancer Society (RSG-09-015-01-CDD), the National Cancer Institute at the National Institutes of Health (1R21CA13345-01/ 1R21CA128414-01A2/UI Mayo Clinic Lymphoma SPORE), and the Pharmaceutical Research and Manufacturers of America (PhRMA) Foundation. C. Lemke acknowledges support from the PhRMA foundation for a post-doctoral fellowship, and Y. Krishnamachari acknowledges support from a Guillory Fellowship.

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  1. Department of Pharmaceutical Sciences & Experimental Therapeutics College of Pharmacy, University of Iowa, Iowa City, Iowa, 52242, USA

    Yogita Krishnamachari, Sean M. Geary, Caitlin D. Lemke & Aliasger K. Salem

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  1. Yogita Krishnamachari
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  2. Sean M. Geary
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Correspondence to Aliasger K. Salem.

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Yogita Krishnamachari, Sean M. Geary and Caitlin D. Lemke have contributed equally.

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Krishnamachari, Y., Geary, S.M., Lemke, C.D. et al. Nanoparticle Delivery Systems in Cancer Vaccines. Pharm Res 28, 215–236 (2011). https://doi.org/10.1007/s11095-010-0241-4

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