149
Views
5
CrossRef citations to date
0
Altmetric
Review

Lipid-based delivery of CpG oligodeoxynucleotides for cancer immunotherapy

&
Pages 181-193 | Published online: 10 Jan 2014

References

  • Bui JD, Schreiber RD. Cancer immunosurveillance, immunoediting and inflammation: independent or interdependent processes? Curr. Opin. Immunol.19(2), 203–208 (2007).
  • Zitvogel L, Tesniere A, Kroemer G. Cancer despite immunosurveillance: immunoselection and immunosubversion. Nat. Rev. Immunol.6(10), 715–727 (2006).
  • Baron F, Storb R. Allogeneic hematopoietic cell transplantation as treatment for hematological malignancies: a review. Springer Semin. Immunopathol.26(1–2), 71–94 (2004).
  • Sprangers B, Fevery S, Van Wijmeersch B, De Somer L, Waer M, Billiau AD. Can graft-versus-leukemia reactivity be dissociated from graft-versus-host disease? Front. Biosci.12, 4568–4594 (2007).
  • Loren AW, Porter DL. Donor leukocyte infusions for the treatment of relapsed acute leukemia after allogeneic stem cell transplantation. Bone Marrow Transplant.41(5), 483–493 (2008).
  • Hemmi H, Takeuchi O, Kawai T et al. A Toll-like receptor recognizes bacterial DNA. Nature408(6813), 740–745 (2000).
  • Takeshita F, Leifer CA, Gursel I et al. Cutting edge: role of Toll-like receptor 9 in CpG DNA-induced activation of human cells. J. Immunol.167(7), 3555–3558 (2001).
  • Krieg AM. Mechanisms and applications of immune stimulatory CpG oligodeoxynucleotides. Biochim. Biophys. Acta1489(1), 107–116 (1999).
  • Friedberg JW, Kim H, McCauley M et al. Combination immunotherapy with a CpG oligonucleotide (1018 ISS) and rituximab in patients with non-Hodgkin’s lymphoma: increased interferon-α/β-inducible gene expression, without significant toxicity. Blood105(2), 489–495 (2005).
  • Klinman DM, Kamstrup S, Verthelyi D et al. Activation of the innate immune system by CpG oligodeoxynucleotides: immunoprotective activity and safety. Springer Semin. Immunopathol.22(1–2), 173–183 (2000).
  • Weigel BJ, Rodeberg DA, Krieg AM,Blazar BR. CpG oligodeoxynucleotides potentiate the antitumor effects of chemotherapy or tumor resection in an orthotopic murine model of rhabdomyosarcoma. Clin. Cancer Res.9(8), 3105–3114 (2003).
  • Krieg AM. Antitumor applications of stimulating toll-like receptor 9 with CpG oligodeoxynucleotides. Curr. Oncol. Rep.6(2), 88–95 (2004).
  • Tam Y. Liposome encapsulation enhances the activity of immunostimulatory oligonucleotides. Future Lipidol.1(1), 35–46 (2006).
  • Krieg AM, Efler SM, Wittpoth M, Al Adhami MJ, Davis HL. Induction of systemic TH1-like innate immunity in normal volunteers following subcutaneous but not intravenous administration of CPG 7909, a synthetic B-class CpG oligodeoxynucleotide TLR9 agonist. J. Immunother.27(6), 460–471 (2004).
  • Moore DJ, Hwang J, McGreivy J et al. Phase I trial of escalating doses of the TLR9 agonist HYB2055 in patients with advanced solid tumors. Presented at: 41st ASCO Annual Meeting. Orlando, FL, USA, 13–17 May 2005.
  • Leichman G, Gravenor D, Woytowitz D et al. CpG 7909, a TLR9 agonist, added to first line taxane/platinum for advanced non-small cell lung cancer, a randomized, controlled Phase II study. Presented at: 41st ASCO Annual Meeting. Orlando, FL, USA, 13–17 May 2005.
  • Speiser DE, Lienard D, Rufer N et al. Rapid and strong human CD8+ T cell responses to vaccination with peptide, IFA, and CpG oligodeoxynucleotide 7909. J. Clin. Invest.115(3), 739–746 (2005).
  • Wagner S, Weber J, Redman B et al. CPG 7909, a TLR9 agonist in metastatic melanoma: a randomized Phase II trial comparing two doses and in combination with DTIC. Presented at: 41st ASCO Annual Meeting. Orlando, FL, USA, 13–17 May 2005.
  • Weiner GJ. Immunostimulatory DNA sequences and cancer therapy. Springer Semin. Immunopathol.22(1–2), 107–116 (2000).
  • Kurreck J. Antisense technologies. Improvement through novel chemical modifications. Eur. J. Biochem.270(8), 1628–1644 (2003).
  • Levin AA. A review of the issues in the pharmacokinetics and toxicology of phosphorothioate antisense oligonucleotides. Biochim. Biophys. Acta1489(1), 69–84 (1999).
  • Henry SP, Monteith D, Levin AA. Antisense oligonucleotide inhibitors for the treatment of cancer: 2. Toxicological properties of phosphorothioate oligodeoxynucleotides. Anticancer Drug Des.12(5), 395–408 (1997).
  • Marquis JK, Grindel JM. Toxicological evaluation of oligonucleotide therapeutics. Curr. Opin. Mol. Ther.2(3), 258–263 (2000).
  • Kindrachuk J, Potter JE, Brownlie R et al. Nucleic acids exert a sequence-independent cooperative effect on sequence-dependent activation of Toll-like receptor 9. J. Biol. Chem.282(19), 13944–13953 (2007).
  • Krieg AM. CpG motifs in bacterial DNA and their immune effects. Annu. Rev. Immunol.20, 709–760 (2002).
  • Bauer S, Kirschning CJ, Hacker H et al. Human TLR9 confers responsiveness to bacterial DNA via species-specific CpG motif recognition. Proc. Natl Acad. Sci. USA98(16), 9237–9242 (2001).
  • Haas T, Metzger J, Schmitz F et al. The DNA sugar backbone 2´ deoxyribose determines Toll-like receptor 9 activation. Immunity28(3), 315–323 (2008).
  • Latz E, Schoenemeyer A, Visintin A et al. TLR9 signals after translocating from the ER to CpG DNA in the lysosome. Nat. Immunol.5(2), 190–198 (2004).
  • Yasuda K, Rutz M, Schlatter B et al. CpG motif-independent activation of TLR9 upon endosomal translocation of “natural” phosphodiester DNA. Eur. J. Immunol.36(2), 431–436 (2006).
  • Agrawal S, Temsamani J, Galbraith W, Tang J. Pharmacokinetics of antisense oligonucleotides. Clin. Pharmacokinet.28(1), 7–16 (1995).
  • Sands H, Gorey-Feret LJ, Cocuzza AJ, Hobbs FW, Chidester D, Trainor GL. Biodistribution and metabolism of internally 3H-labeled oligonucleotides. I. Comparison of a phosphodiester and a phosphorothioate. Mol. Pharmacol.45(5), 932–943 (1994).
  • Zhao Q, Matson S, Herrera CJ, Fisher E, Yu H, Krieg AM. Comparison of cellular binding and uptake of antisense phosphodiester, phosphorothioate, and mixed phosphorothioate and methylphosphonate oligonucleotides. Antisense Res. Dev.3(1), 53–66 (1993).
  • Yasuda K, Yu P, Kirschning CJ et al. Endosomal translocation of vertebrate DNA activates dendritic cells via TLR9-dependent and -independent pathways. J. Immunol.174(10), 6129–6136 (2005).
  • Allen TM, Cullis PR. Drug delivery systems: entering the mainstream. Science303(5665), 1818–1822 (2004).
  • Wagner V, Dullaart A, Bock AK, Zweck A. The emerging nanomedicine landscape. Nat. Biotechnol.24(10), 1211–1217 (2006).
  • Matsumura Y, Maeda H. A new concept for macromolecular therapeutics in cancer chemotherapy: mechanism of tumoritropic accumulation of proteins and the antitumor agent smancs. Cancer Res.46(12 Pt 1), 6387–6392 (1986).
  • Maurer N, Fenske DB, Cullis PR. Developments in liposomal drug delivery systems. Expert Opin. Biol. Ther.1(6), 923–947 (2001).
  • Storni T, Ruedl C, Schwarz K, Schwendener RA, Renner WA, Bachmann MF. Nonmethylated CG motifs packaged into virus-like particles induce protective cytotoxic T cell responses in the absence of systemic side effects. J. Immunol.172(3), 1777–1785 (2004).
  • Song S, Wang Y, Zhang Y et al. Augmented induction of CD8+ cytotoxic T-cell response and antitumor effect by DCs pulsed with virus-like particles packaging with CpG. Cancer Lett.256(1), 90–100 (2007).
  • Semple SC, Klimuk SK, Harasym TO, Hope MJ. Lipid-based formulations of antisense oligonucleotides for systemic delivery applications. Methods Enzymol.313, 322–341 (2000).
  • Bally MB, Harvie P, Wong FM, Kong S, Wasan EK, Reimer DL. Biological barriers to cellular delivery of lipid-based DNA carriers. Adv. Drug Deliv. Rev.38(3), 291–315 (1999).
  • Maurer N, Wong KF, Stark H et al. Spontaneous entrapment of polynucleotides upon electrostatic interaction with ethanol-destabilized cationic liposomes. Biophys. J.80(5), 2310–2326 (2001).
  • Thierry AR, Dritschilo A. Intracellular availability of unmodified, phosphorothioated and liposomally encapsulated oligodeoxynucleotides for antisense activity. Nucleic Acids Res.20(21), 5691–5698 (1992).
  • Meyer O, Kirpotin D, Hong K et al. Cationic liposomes coated with polyethylene glycol as carriers for oligonucleotides. J. Biol. Chem.273(25), 15621–15627 (1998).
  • Mahato RI, Anwer K, Tagliaferri F et al. Biodistribution and gene expression of lipid/plasmid complexes after systemic administration. Hum. Gene Ther.9(14), 2083–2099 (1998).
  • Tousignant JD, Gates AL, Ingram LA et al. Comprehensive analysis of the acute toxicities induced by systemic administration of cationic lipid:plasmid DNA complexes in mice. Hum. Gene Ther.11(18), 2493–2513 (2000).
  • Loisel S, Le Gall C, Doucet L, Ferec C, Floch V. Contribution of plasmid DNA to hepatotoxicity after systemic administration of lipoplexes. Hum. Gene Ther.12(6), 685–696 (2001).
  • Tan Y, Liu F, Li Z, Li S, Huang L. Sequential injection of cationic liposome and plasmid DNA effectively transfects the lung with minimal inflammatory toxicity. Mol. Ther.3(5 Pt 1), 673–682 (2001).
  • Dokka S, Toledo D, Shi X, Castranova V, Rojanasakul Y. Oxygen radical-mediated pulmonary toxicity induced by some cationic liposomes. Pharm. Res.17(5), 521–525 (2000).
  • Eliyahu H, Servel N, Domb AJ, Barenholz Y. Lipoplex-induced hemagglutination: potential involvement in intravenous gene delivery. Gene Ther.9(13), 850–858 (2002).
  • Barron LG, Meyer KB, Szoka FC Jr. Effects of complement depletion on the pharmacokinetics and gene delivery mediated by cationic lipid-DNA complexes. Hum. Gene Ther.9(3), 315–323 (1998).
  • Wright MJ, Rosenthal E, Stewart L et al. β-galactosidase staining following intracoronary infusion of cationic liposomes in the in vivo rabbit heart is produced by microinfarction rather than effective gene transfer: a cautionary tale. Gene Ther.5(3), 301–308 (1998).
  • Chiou HC, Tangco MV, Levine SM et al. Enhanced resistance to nuclease degradation of nucleic acids complexed to asialoglycoprotein-polylysine carriers. Nucleic Acids Res.22(24), 5439–5446 (1994).
  • Dash PR, Read ML, Barrett LB, Wolfert MA, Seymour LW. Factors affecting blood clearance and in vivodistribution of polyelectrolyte complexes for gene delivery. Gene Ther.6(4), 643–650 (1999).
  • Hwang SJ, Davis ME. Cationic polymers for gene delivery: designs for overcoming barriers to systemic administration. Curr. Opin. Mol. Ther.3(2), 183–191 (2001).
  • Faneca H, Simoes S, de Lima MC. Evaluation of lipid-based reagents to mediate intracellular gene delivery. Biochim. Biophys. Acta1567(1–2), 23–33 (2002).
  • Bonte F, Juliano RL. Interactions of liposomes with serum proteins. Chem. Phys. Lipids40(2–4), 359–372 (1986).
  • de Jong S, Chikh G, Sekirov L et al. Encapsulation in liposomal nanoparticles enhances the immunostimulatory, adjuvant and anti-tumor activity of subcutaneously administered CpG ODN. Cancer Immunol. Immunother.56(8), 1251–1264 (2007).
  • Wilson KD, Raney SG, Sekirov L et al. Effects of intravenous and subcutaneous administration on the pharmacokinetics, biodistribution, cellular uptake and immunostimulatory activity of CpG ODN encapsulated in liposomal nanoparticles. Int. Immunopharmacol.7(8), 1064–1075 (2007).
  • Hope MJ, Mui B, Ansell S, Ahkong QF. Cationic lipids, phosphatidylethanolamine and the intracellular delivery of polymeric, nucleic acid-based drugs (review). Mol. Membr. Biol.15(1), 1–14 (1998).
  • Yu RZ, Geary RS, Leeds JM et al. Comparison of pharmacokinetics and tissue disposition of an antisense phosphorothioate oligonucleotide targeting human Ha-ras mRNA in mouse and monkey. J. Pharm. Sci.90(2), 182–193 (2001).
  • Wingender G, Garbi N, Schumak B et al. Systemic application of CpG-rich DNA suppresses adaptive T cell immunity via induction of IDO. Eur. J. Immunol.36(1), 12–20 (2006).
  • Heckelsmiller K, Beck S, Rall K et al. Combined dendritic cell- and CpG oligonucleotide-based immune therapy cures large murine tumors that resist chemotherapy. Eur. J. Immunol.32(11), 3235–3245 (2002).
  • Kawarada Y, Ganss R, Garbi N, Sacher T, Arnold B, Hammerling GJ. NK- and CD8+ T cell-mediated eradication of established tumors by peritumoral injection of CpG-containing oligodeoxynucleotides. J. Immunol.167(9), 5247–5253 (2001).
  • Semple SC, Klimuk SK, Harasym TO et al. Efficient encapsulation of antisense oligonucleotides in lipid vesicles using ionizable aminolipids: formation of novel small multilamellar vesicle structures. Biochim. Biophys. Acta1510(1–2), 152–166 (2001).
  • Capaccioli S, Di Pasquale G, Mini E, Mazzei T, Quattrone A. Cationic lipids improve antisense oligonucleotide uptake and prevent degradation in cultured cells and in human serum. Biochem. Biophys. Res. Commun.197(2), 818–825 (1993).
  • Mui B, Raney SG, Semple SC, Hope MJ. Immune stimulation by a CpG-containing oligodeoxynucleotide is enhanced when encapsulated and delivered in lipid particles. J. Pharmacol. Exp. Ther.298(3), 1185–1192 (2001).
  • Whitmore MM, Li S, Falo L Jr, Huang L. Systemic administration of LPD prepared with CpG oligonucleotides inhibits the growth of established pulmonary metastases by stimulating innate and acquired antitumor immune responses. Cancer Immunol. Immunother.50(10), 503–514 (2001).
  • Chesnoy S, Huang L. Structure and function of lipid-DNA complexes for gene delivery. Annu. Rev. Biophys. Biomol. Struct.29, 27–47 (2000).
  • Lee KD, Nir S, Papahadjopoulos D. Quantitative analysis of liposome-cell interactions in vitro: rate constants of binding and endocytosis with suspension and adherent J774 cells and human monocytes. Biochemistry32(3), 889–899 (1993).
  • Gursel I, Gursel M, Ishii KJ, Klinman DM. Sterically stabilized cationic liposomes improve the uptake and immunostimulatory activity of CpG oligonucleotides. J. Immunol.167(6), 3324–3328 (2001).
  • Yasuda K, Ogawa Y, Yamane I, Nishikawa M, Takakura Y. Macrophage activation by a DNA/cationic liposome complex requires endosomal acidification and TLR9-dependent and -independent pathways. J. Leukoc. Biol.77(1), 71–79 (2005).
  • 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.145, 5–31 (1995).
  • Gregoriadis G. Liposomes as immunoadjuvants and vaccine carriers: antigen entrapment. Immunomethods4(3), 210–216 (1994).
  • Suzuki Y, Wakita D, Chamoto K et al. Liposome-encapsulated CpG oligodeoxynucleotides as a potent adjuvant for inducing type 1 innate immunity. Cancer Res.64(23), 8754–8760 (2004).
  • Marciani DJ. Vaccine adjuvants: role and mechanisms of action in vaccine immunogenicity. Drug Discov. Today8(20), 934–943 (2003).
  • Khazanov E, Simberg D, Barenholz Y. Lipoplexes prepared from cationic liposomes and mammalian DNA induce CpG-independent, direct cytotoxic effects in cell cultures and in mice. J. Gene Med.8(8), 998–1007 (2006).
  • Raney SG, Sekirov L, DeJong SD, Brodsky II, Chikh G, Tam YK. Methylated CpG ODNs are potent adjuvants when encapsulated in stablized lipid particles. Presented at: 12th International Conference of Immunology and 4th Annual Conference of FOCIS. Montreal, Canada, 18–23 July 2004.
  • Tam YK, deJong SD, Basha G, Wilson KD, Kazem M, Cullis P. Lipid encapsulation promotes co-localization of methylated CpG ODN and TLR9 in late endosomes: a new model for the immunostimulatory activity of CpG DNA. Presented at: 99th Annual AACR Meeting. San Diego, CA, USA, 12–16 April 2008.
  • Lanuti M, Rudginsky S, Force SD et al. Cationic lipid:bacterial DNA complexes elicit adaptive cellular immunity in murine intraperitoneal tumor models. Cancer Res.60(11), 2955–2963 (2000).
  • Lonsdorf AS, Kuekrek H, Stern BV, Boehm BO, Lehmann PV, Tary-Lehmann M. Intratumor CpG-oligodeoxynucleotide injection induces protective antitumor T cell immunity. J. Immunol.171(8), 3941–3946 (2003).
  • Baines J, Celis E. Immune-mediated tumor regression induced by CpG-containing oligodeoxynucleotides. Clin. Cancer Res.9(7), 2693–2700 (2003).
  • Mutwiri GK, Nichani AK, Babiuk S, Babiuk LA. Strategies for enhancing the immunostimulatory effects of CpG oligodeoxynucleotides. J. Control. Release97(1), 1–17 (2004).
  • 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.163(3), 1552–1561 (1999).
  • Whitmore M, Li S, Huang L. LPD lipopolyplex initiates a potent cytokine response and inhibits tumor growth. Gene Ther.6(11), 1867–1875 (1999).
  • Sakurai F, Terada T, Maruyama M et al. Therapeutic effect of intravenous delivery of lipoplexes containing the interferon-β gene and poly I: poly C in a murine lung metastasis model. Cancer Gene Ther.10(9), 661–668 (2003).
  • Sturlan S, Schneeberger A, Fang M et al. Intraperitoneal administration of pMP6/liposome complexes inhibits the growth of co-localized colon-26 adenocarcinoma cells by inducing a tumor-specific immune response. Anticancer Res.23(6C), 4843–4851 (2003).
  • Ishii KJ, Kawakami K, Gursel I et al. Antitumor therapy with bacterial DNA and toxin: complete regression of established tumor induced by liposomal CpG oligodeoxynucleotides plus interleukin-13 cytotoxin. Clin. Cancer Res.9(17), 6516–6522 (2003).
  • Higgins RJ, McKisic M, Dickinson PJ et al. Growth inhibition of an orthotopic glioblastoma in immunocompetent mice by cationic lipid-DNA complexes. Cancer Immunol. Immunother.53(4), 338–344 (2004).
  • Brignole C, Pastorino F, Marimpietri D et al. Immune cell-mediated antitumor activities of GD2-targeted liposomal c-myb antisense oligonucleotides containing CpG motifs. J. Natl Cancer Inst.96(15), 1171–1180 (2004).
  • Maloney DG, Grillo-Lopez AJ, White CA et al. IDEC-C2B8 (Rituximab) anti-CD20 monoclonal antibody therapy in patients with relapsed low-grade non-Hodgkin’s lymphoma. Blood90(6), 2188–2195 (1997).
  • Ballas ZK, Rasmussen WL, Krieg AM. Induction of NK activity in murine and human cells by CpG motifs in oligodeoxynucleotides and bacterial DNA. J. Immunol.157(5), 1840–1845 (1996).
  • Weiner GJ, Link BK, Leonard J, Emmanouilides C, Albert G, Schmalbach T. Combination of CpG7909 and rituximab in patients with relapsed or refractory B-cell non-Hodgkin’s lymphoma (NHL): a Phase I, open label dose-escalation study of safety and tolerability. Presented at: 40th ASCO Annual Meeting. New Orleans, LA, USA, 5–8 June 2004.
  • Villamor N, Montserrat E, Colomer D. Mechanism of action and resistance to monoclonal antibody therapy. Semin. Oncol.30(4), 424–433 (2003).
  • Roda JM, Parihar R, Carson WE 3rd. CpG-containing oligodeoxynucleotides act through TLR9 to enhance the NK cell cytokine response to antibody-coated tumor cells. J. Immunol.175(3), 1619–1627 (2005).
  • van Ojik HH, Bevaart L, Dahle CE et al. CpG-A and B oligodeoxynucleotides enhance the efficacy of antibody therapy by activating different effector cell populations. Cancer Res.63(17), 5595–5600 (2003).
  • Warren TL, Dahle CE, Weiner GJ. CpG oligodeoxynucleotides enhance monoclonal antibody therapy of a murine lymphoma. Clin. Lymphoma1(1), 57–61 (2000).
  • Leonard JP, Link BK, Emmanouilides C et al. Phase I trial of Toll-like receptor 9 agonist PF-3512676 with and following rituximab in patients with recurrent indolent and aggressive non Hodgkin’s lymphoma. Clin. Cancer Res.13(20), 6168–6174 (2007).
  • Moga E, Alvarez E, Canto E et al. NK cells stimulated with IL-15 or CpG ODN enhance rituximab-dependent cellular cytotoxicity against B-cell lymphoma. Exp. Hematol.36(1), 69–77 (2008).
  • Sekirov L, Brodsky II, Raney SG, Chikh G, Tam YK. Intravenous administration of a liposomal CpG ODN (INX-0167) activates NK cells and potentiates ADCC. Presented at: 12th International Conference of Immunology and 4th Annual Conference of FOCIS. Montreal, Canada, 18–23 July 2004.
  • Tam YK, Sekirov L, Raney S, Brodsky II, Chikh G. Liposomal encapsulation enhances the immunopotency of CpG ODN and potentiates ADCC by activation, expansion and enhanced homing of NK cells. Presented at: 97th Annual AACR Meeting. Washington, DC, USA, 1–5 April 2006.
  • Vicari AP, Luu R, Zhang N et al. Paclitaxel reduces regulatory T cell numbers and inhibitory function and enhances the anti-tumor effects of the TLR9 agonist PF-3512676 in the mouse. Cancer Immunol. Immunother.58(4), 615–628 (2009).
  • Joseph A, Louria-Hayon I, Plis-Finarov A et al. Liposomal immunostimulatory DNA sequence (ISS-ODN): an efficient parenteral and mucosal adjuvant for influenza and hepatitis B vaccines. Vaccine20(27–28), 3342–3354 (2002).
  • Yoshikawa T, Imazu S, Gao JQ et al. Non-methylated CpG motif packaged into fusogenic liposomes enhance antigen-specific immunity in mice. Biol. Pharm. Bull.29(1), 105–109 (2006).
  • Zaks K, Jordan M, Guth A et al. Efficient immunization and cross-priming by vaccine adjuvants containing TLR3 or TLR9 agonists complexed to cationic liposomes. J. Immunol.176(12), 7335–7345 (2006).
  • Cui Z, Han SJ, Vangasseri DP, Huang L. Immunostimulation mechanism of LPD nanoparticle as a vaccine carrier. Mol. Pharm.2(1), 22–28 (2005).
  • Wakita D, Chamoto K, Zhang Y et al. An indispensable role of type-1 IFNs for inducing CTL-mediated complete eradication of established tumor tissue by CpG-liposome co-encapsulated with model tumor antigen. Int. Immunol.18(3), 425–434 (2006).
  • Lollini PL, De Giovanni C, Nicoletti G et al. Enhancement of experimental metastatic ability by tumor necrosis factor-α alone or in combination with interferon-γ. Clin. Exp. Metastasis8(2), 215–224 (1990).
  • Li WM, Dragowska WH, Bally MB, Schutze-Redelmeier MP. Effective induction of CD8+ T-cell response using CpG oligodeoxynucleotides and HER-2/neu-derived peptide co-encapsulated in liposomes. Vaccine21(23), 3319–3329 (2003).
  • Jerome V, Graser A, Muller R, Kontermann RE, Konur A. Cytotoxic T lymphocytes responding to low dose TRP2 antigen are induced against B16 melanoma by liposome-encapsulated TRP2 peptide and CpG DNA adjuvant. J. Immunother.29(3), 294–305 (2006).
  • Schuster M, Nechansky A, Kircheis R. Cancer immunotherapy. Biotechnol. J.1(2), 138–147 (2006).
  • Ryan SO, Gantt KR, Finn OJ. Tumor antigen-based immunotherapy and immunoprevention of cancer. Int. Arch. Allergy Immunol.142(3), 179–189 (2007).
  • Krieg AM. Development of TLR9 agonists for cancer therapy. J. Clin. Invest.117(5), 1184–1194 (2007).
  • Gregoriadis G. The immunological adjuvant and vaccine carrier properties of liposomes. J. Drug Target.2(5), 351–356 (1994).
  • Chen WC, Huang L. Non-viral vector as vaccine carrier. Adv. Genet.54, 315–337 (2005).

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.