• 1
    American Cancer Society. 2008. Available at: Accessed on June 4, 2008.
  • 2
    Cunningham D,Pyrhonen S,James RD,Punt CJ,Hickish TF,Heikkila R,Johannesen TB,Starkhammar H,Topham CA,Awad L,Jacques C,Herait P. Randomised trial of irinotecan plus supportive care versus supportive care alone after fluorouracil failure for patients with metastatic colorectal cancer. Lancet 1998; 352: 141318.
  • 3
    de Gramont A,Figer A,Seymour M,Homerin M,Hmissi A,Cassidy J,Boni C,Cortes-Funes H,Cervantes A,Freyer G,Papamichael D,Le Bail N, et al. Leucovorin and fluorouracil with or without oxaliplatin as first-line treatment in advanced colorectal cancer. J Clin Oncol 2000; 18: 293847.
  • 4
    Saltz LB,Cox JV,Blanke C,Rosen LS,Fehrenbacher L,Moore MJ,Maroun JA,Ackland SP,Locker PK,Pirotta N,Elfring GL,Miller LL. Irinotecan plus fluorouracil and leucovorin for metastatic colorectal cancer. Irinotecan Study Group. N Engl J Med 2000; 343: 90514.
  • 5
    Engstrom PF,Benson A,Saltz L. The NCCN colon cancer clinical practice guidelines in oncology. JNCCN 2003; 1: 4053.
  • 6
    Gilboa E. The makings of a tumor rejection antigen. Immunity 1999; 11: 26370.
  • 7
    Ochsenbein AF. Principles of tumor immunosurveillance and implications for immuno-therapy. Cancer Gene Ther 2002; 9: 104355.
  • 8
    Banchereau J,Briere F,Caux C,Davoust J,Lebecque S,Liu YJ,Pulendran B,Palucka K. Immunobiology of dendritic cells. Annu Rev Immunol 2000; 18: 767811.
  • 9
    Schreurs MW,Eggert AA,Punt CJ,Figdor CG,Adema GJ. Dendritic cell-based vaccines: from mouse models to clinical cancer immunotherapy. Crit Rev Oncog 2000; 11: 117.
  • 10
    Engleman EG. Dendritic cell-based cancer immunotherapy. Semin Oncol 2003; 30( 3 Suppl. 8, ): 239.
  • 11
    Ridgway D. The first 1000 dendritic cell vaccines. Cancer Invest 2003; 21: 87386.
  • 12
    Dranoff G,Jaffee E,Lazenby A,Golumbek P,Levitsky H,Brose K,Jackson V,Hamada H,Pardoll D,Mulligan RC. Vaccination with irradiated tumor cells engineered to secrete murine granulocyte-macrophage colony-stimulating factor stimulates potent, specific, and long-lasting anti-tumor immunity. Proc Natl Acad Sci USA 1993; 90: 353943.
  • 13
    Chen K,Braun S,Lyman S,Fan Y,Traycoff CM,Wiebke EA,Gaddy J,Sledge G,Broxmeyer HE,Cornetta K. Antitumor activity and immunotherapeutic properties of Flt3-ligand in a murine breast cancer model. Cancer Res 1997; 57: 351116.
  • 14
    Shimizu K,Fields RC,Gieldlin M,Mule JJ. Systemic administration of interleukin 2 enhances the therapeutic efficacy of dendritic cell-based tumor vaccines. Proc Natl Acad Sci USA 1999; 96: 226873.
  • 15
    Fallarino F,Uyttenhove C,Boon T,Gajewski TF. Improved efficacy of dendritic cell vaccines and successful immunization with tumor antigen peptide-pulsed peripheral blood mononuclear cells by coadministration of recombinant murine interleukin-12. Int J Cancer 1999; 80: 32433.
  • 16
    Krieg AM,Yi AK,Matson S,Waldschmidt TJ,Bishop GA,Teasdale R,Koretzky GA,Klinman DM. CpG motifs in bacterial DNA trigger direct B-cell activation. Nature 1995; 374: 5469.
  • 17
    Krieg AM. CpG motifs: the active ingredient in bacterial extracts? Nat Med 2003; 9: 8315.
  • 18
    Akira S,Takeda K,Kaisho T. Toll-like receptors: critical proteins linking innate and acquired immunity. Nat Immunol 2001; 2: 67580.
  • 19
    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. JImmunol 2001; 167: 524753.
  • 20
    Baines J,Celis E. Immune-mediated tumor regression induced by CpG-containing oligodeoxynucleotides. Clin Cancer Res 2003; 9: 2693700.
  • 21
    Pilon-Thomas S,Li W,Briggs JJ,Djeu J,Mule JJ,Riker AI. Immunostimulatory effects of CpG-ODN upon dendritic cell-based immunotherapy in a murine melanoma model. J Immunother 2006; 29: 3817.
  • 22
    Heckelsmiller K,Beck S,Rall K,Sipos B,Schlamp A,Tuma E,Rothenfusser S,Endres S,Hartmann G. Combined dendritic cell- and CpG oligonucleotide-based immune therapy cures large murine tumors that resist chemotherapy. Eur J Immunol 2002; 32: 323545.
  • 23
    Milas L,Mason KA,Ariga H,Hunter N,Neal R,Valdecanas D,Krieg AM,Whisnant JK. CpG oligodeoxynucleotide enhances tumor response to radiation. Cancer Res 2004; 64: 50747.
  • 24
    Wooldridge JE,Ballas Z,Krieg AM,Weiner GJ. Immunostimulatory oligodeoxynucleotides containing CpG motifs enhance the efficacy of monoclonal antibody therapy of lymphoma. Blood 1997; 89: 29948.
  • 25
    Whitmore MM,DeVeer MJ,Edling A,Oates RK,Simons B,Lindner D,Williams BR. Synergistic activation of innate immunity by double-stranded RNA and CpG DNA promotes enhanced antitumor activity. Cancer Res 2004; 64: 585060.
  • 26
    Jiang W,Pisetsky DS. Enhancing immuno-genicity by CpG DNA. Curr Opin Mol Ther 2003; 5: 1805.
  • 27
    Saha A,Chatterjee SK,Foon KA,Celis E,Bhattacharya-Chatterjee M. Therapy of established tumors in a novel murine model transgenic for human carcinoembryonic antigen and HLA-A2 with a combination of anti-idiotype vaccine and CTL peptides of carcinoembryonic antigen. Cancer Res 2007; 67: 288192.
  • 28
    Clarke P,Mann J,Simpson JF,Rickard-Dickson K,Primus FJ. Mice transgenic for human carcinoembryonic antigen as a model for immunotherapy. Cancer Res 1998; 58: 146977.
  • 29
    Kawashima I,Hudson SJ,Tsai V,Southwood S,Takesako K,Appella E,Sette A,Celis E. The multi-epitope approach for immunotherapy for cancer: identification of several CTL epitopes from various tumor-associated antigens expressed on solid epithelial tumors. Hum Immunol 1998; 59: 114.
  • 30
    Tsang KY,Zaremba S,Nieroda CA,Zhu MZ,Hamilton JM,Schlom J. Generation of human cytotoxic T cells specific for human carcinoembryonic antigen epitopes from patients immunized with recombinant vaccinia-CEA vaccine. J Natl Cancer Inst 1995; 87: 98290.
  • 31
    Lu J,Higashimoto Y,Appella E,Celis E. Multiepitope Trojan antigen peptide vaccines for the induction of antitumor CTL and Th immune responses. J Immunol 2004; 172: 457582.
  • 32
    Cho DH,Song HK,Kang HS,Yoon SR,Lee HG,Pyun KH,Lee WJ,Kim YB,Choi I. Ligation of ICAM-1 molecules inhibits target cell-induced granule exocytosis of IL-12-activated natural killer cells. Cell Immunol 2000; 199: 17.
  • 33
    Kataoka T,Shinohara N,Takayama H,Takaku K,Kondo S,Yonehara S,Nagai K. Concanamycin A, a powerful tool for characterization and estimation of contribution of perforin- and Fas-based lytic pathways in cell-mediated cytotoxicity. J Immunol 1996; 156: 367886.
  • 34
    Uhlmann E,Vollmer J. Recent advances in the development of immunostimulatory oligonucleotides. Curr Opin Drug Discov Dev 2003; 6: 20417.
  • 35
    Walunas TL,Bruce DS,Dustin L,Loh DY,Bluestone JA. Ly-6C is a marker of memory CD8+ T cells. J Immunol 1995; 155: 187383.
  • 36
    Curtsinger JM,Lins DC,Mescher MF. CD8+ memory T cells (CD44high, Ly-6C+) are more sensitive than naïve cells (CD44low, Ly-6C-) to TCR/CD8 signaling in response to antigen. J Immunol 1998; 160: 323643.
  • 37
    Krieg AM. CpG motifs in bacterial DNA and their immune effects. Annu Rev Immunol 2002; 20: 70960.
  • 38
    Heckelsmiller K,Rall K,Beck S,Schlamp A,Seiderer J,Jahrsdorfer B,Krug A,Rothenfusser S,Endres S,Hartmann G. Peritumoral CpG DNA elicits a coordinated response of CD8 T cells and innate effectors to cure established tumors in a murine colon carcinoma model. JImmunol 2002; 169: 38929.
  • 39
    Chu RS,Targoni OS,Krieg AM,Lehmann PV,Harding CV. CpG oligodeoxynucleotides acts as adjuvants that switch on T helper 1 (Th1) immunity. J Exp Med 1997; 186: 162331.
  • 40
    Warren TL,Bhatia SK,Acosta AM,Dahle CE,Ratliff TL,Krieg AM,Weiner GJ. APC stimulated by CpG oligodeoxynucleotide enhance activation of MHC class I-restricted T cells. J Immunol 2000; 165: 624451.
  • 41
    Brunner C,Seiderer J,Schlamp A,Bidlingmaier M,Eigler A,Haimerl W,Lehr HA,Krieg AM,Hartmann G,Endres S. Enhanced dendritic cell maturation by TNF-α or cytidine-phosphate-guanosine DNA drives T cell activation in vitro and therapeutic anti-tumor immune responses in vivo. J Immunol 2000; 165: 627886.
  • 42
    Davila E,Celis E. Repeated administration of cytosine-phosphorothiolated guanine-containing oligonucleotides together with peptide/protein immunization results in enhanced CTL responses with anti-tumor activity. J Immunol 2000; 165: 53947.
  • 43
    Liu HM,Newbrough SE,Bhatia SK,Dahle CE,Krieg AM,Weiner GJ. Immunostimulatory CpG oligodeoxynucleotides enhance the immune response to vaccine strategies involving granulocyte-macrophage colony-stimulating factor. Blood 1998; 92: 37306.
  • 44
    Sandler AD,Chihara H,Kobayashi G,Zhu X,Miller MA,Scott DL,Krieg AM. CpG oligonucleotides enhance the tumor antigen-specific immune response of a granulocyte macrophage colony-stimulating factor-based vaccine strategy in neuroblastoma. Cancer Res 2003; 63: 3949.
  • 45
    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 1996; 157: 18405.
  • 46
    Krieg AM,Love-Homan L,Yi AK,Harty JT. CpG DNA induces sustained IL-12 expression in vivo and resistance to Listeria monocytogenes challenge. J Immunol 1998; 161: 242834.
  • 47
    Lanier LL. Follow the leader: NK cell receptors for classical and nonclassical MHC class I. Cell 1998; 92: 7057.
  • 48
    Grohmann U,Belladonna ML,Bianchi R,Orabona C,Ayroldi E,Fioretti MC,Puccetti P. IL-12 acts directly on DC to promote nuclear localization of NF-κB and primes DC for IL-12 production. Immunity 1998; 9: 31523.
  • 49
    Oppmann B,Lesley R,Blom B,Timans JC,Xu Y,Hunte B,Vega F,Yu N,Wang J,Singh K,Zonin F,Vaisberg E, et al. Novel p19 protein engages IL-12p40 to form a cytokine, IL-23, with biological activities similar as well as distinct from IL-12. Immunity 2000; 13: 71525.
  • 50
    Davila E,Velez MG,Heppelmann CJ,Celis E. Creating space: an antigen-independent, CpG-induced peripheral expansion of naïve and memory T lymphocytes in a full T-cell compartment. Blood 2002; 100: 253745.
  • 51
    Beloeil L,Tomkowiak M,Angelov G,Walzer T,Dubois P,Marvel J. In vivo impact of CpG 1826 oligodeoxynucleotide on CD8 T cell primary responses and survival. J Immunol 2003; 171: 29953002.
  • 52
    Lu J,Giuntoli RLJr,Omiya R,Kobayashi H,Kennedy R,Celis E. Interleukin 15 promotes antigen-independent in vitro expansion and long-term survival of antitumor cytotoxic T lymphocytes. Clin Cancer Res 2002; 8: 387784.
  • 53
    Mattei F,Schiavoni G,Belardelli F,Tough DF. IL-15 is expressed by dendritic cells in response to type I IFN, double-stranded RNA, or lipopolysaccharide and promotes dendritic cell activation. J Immunol 2001; 167: 117987.
  • 54
    Cho HJ,Hayashi T,Datta SK,Takabayashi K,VanUden JH,Horner A,Corr M,Raz E. IFN-αβ promote priming of antigen-specific CD8+ and CD4+ T lymphocytes by immunostimulatory DNA-based vaccines. J Immunol 2002; 168: 490713.