Antisense and/or immunostimulatory oligonucleotide therapeutics

Current Cancer Drug Targets

Volumn 1, Issue 3, 2001, Pages 197-209

  Agrawal, Sudhir ^a   Kandimalla, Ekambar R ^a  

^a HYBRIDON INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTINEOPLASTIC AGENT; ANTISENSE OLIGONUCLEOTIDE; IMMUNOLOGICAL ADJUVANT; MESSENGER RNA; NEW DRUG; NUCLEOTIDE; OLIGODEOXYRIBONUCLEOTIDE;

CHEMISTRY; CPG ISLAND; DRUG DESIGN; DRUG SCREENING; GENE EXPRESSION REGULATION; IMMUNOLOGY; NEOPLASM; REVIEW;

ADJUVANTS, IMMUNOLOGIC; ANTINEOPLASTIC AGENTS; CPG ISLANDS; DRUG DESIGN; DRUG EVALUATION, PRECLINICAL; DRUGS, INVESTIGATIONAL; GENE EXPRESSION REGULATION, NEOPLASTIC; NEOPLASMS; OLIGODEOXYRIBONUCLEOTIDES; OLIGONUCLEOTIDES, ANTISENSE; RNA, MESSENGER; THIONUCLEOTIDES;

EID: 0035502598     PISSN: 15680096     EISSN: None     Source Type: Journal    
DOI: 10.2174/1568009013334160     Document Type: Article

References (93)

1. Zamecnik, P. C. InAntisense Therapeutics; Agrawal, S., Ed.; Humana Press: Totowa, NJ, 1996, pp. 1-11.
2. Wickstorm, E., Ed. Clinical Trials of Genetic Therapy with Antisense DNA and DNA Vectors; Marcel Deckker: New York, 1998.
3. Agrawal S.; Zhao Q. Antisense Therapeutics. Curr. Opin. Chem. Biol. 199S,2, 519-528.
4. Bcnnett, C. F. Antisense Oligonucleotides: Is the Glass Half full or Half Empty?. Biochem. Pharmacol. 1998, 55, 9-19.
5. Agrawal S. Importance of Nucleotide Sequence and Chemical Modifications of Antisense Oligonucleotides. Biochim. Biophys. Acta 1999, 1489, 53-68.
6. Agrawa, S.; Kandimalla, E. R. In Antisense Technology in the Central Nervous System; Leslie, R.; Hunter, J.; Robertson, H., Eds.; Oxford University Press: Oxford, 1999, pp132-165.
7. Altmann, K.-H.; Dean, N. M.; Fabbro, D.; Freier, S. M.; Geiger, T.; Haner, R.; Husken, D.; Martin, P.; Monia, B. P.; Muller, M.; Natt, F., Nickiin, P.; Phillips, J.; Pieles, U.; Sasmor, H.; Moser, H. E. Second Generation of Antisense Oligonucleotides: from Nuclease Resistance to Biological Efficacy in Animals. Chimia 1996, 50, 168-176.
8. Seeberger, P. H.; Caruthers, M. H. In Applied Antisense Oligonucleotide Technology; Stein, C. A.; Krieg, A. M., Eds.; Wiley-Liss: New York, 1998, pp. 51-71.
9. Agrawal, S.; Temsamani, J.; Tang, J. Y. Pharmacokinetics, Biodistribution, and Stability of Oligodeoxynucleotide Phosphorothioates in Mice. Proc. Natl. Acad. Sei. USA 1991,55,7595-7599.
10. Agrawal, S.; Temsamani, J.; Galbraith, W.; Tang, J.-Y. Pharmacokinetics of Antisense Oligonucleotides. Clin. Pharmacokinet. 1995,25, 7-16.
11. Agrawal, S. Antisense Oligonucleotides: Towards Clinical Trials. Trends Biotechnoî. 1996, 14, 376-87.
12. Agrawal S.; Zhang R. Pharmacokinetics of Oligonucleotides. Ciba Found Symp. 1997, 209, 60-75.
13. Agrawal S.; Akhtar S. Advances in Antisense Efficacy and Delivery. Trends Biotechnoî. 1995, 13, 197-199.
14. Waters, J. S.; Webb, A.; Cunningham, D.; Clarke, P. A.; Raynaud, F.; diStefano, F.; Cotter, F. E. Phase I Clinical and Pharmacokinetic Study of bcI-2 Antisense Oligonucleotide Therapy in Patients with NonHodgkin's Lymphoma. J. Clin. Oncol. 2000, 75, 18121823.
15. Chen, H. X.; Marshall, J. L.; Ness, E.; Martin, R. R.; Dvorchik, B.; Rizvi, N.; Marquis, J.; McKinlay, M.; Dahut, W.; Hawkins, M. J. A Safety and Pharmacokinetic Study of a Mixed-Backbone Oligonucleotide (GEM231) Targeting the Type I Protein Kinase A by Two-Hour Infusions in Patients with Refractory Solid Tumors. Clin. Cancer Res. 2000, 6, 1259-1266.
16. Rudin, C. M.; Holmlund, J.; Fleming, G. F.; Mani, S.; Stadier, W. M.; Schumm, P.; Monia, B. P.; Johnston, J. F.; Geary, R.; Yu, R. Z.; Kwoh, T. J.; Dorr, F. A.; Ratain, M. J. Phase I Trial of ISIS 5132, an Antisense Oligonucleotide Inhibitor of c-raf-I, Administered by 24-hour Weekly Infusion to Patients with Advanced Cancer. Clin. Cancer Res. 2001, 7, 1214-1220.
17. Cunningham, C. C.; Holmlund, J. T.; Schiller, J. H.; Geary, R. S.; Kwoh, T. J.; Dorr, A.; Nemunaitis, J. A phase I trial of c-Raf Kinase Antisense Oligonucleotide ISIS 5132 Administered as a Continuous Intravenous Infusion in Patients with Advanced Cancer. Clin. Cancer Res. 2000, 6, 1626-1631.
18. O'Dwyer, P. J.; Stevenson, J. P.; Gallagher, M.; Cassella, A.; Vasilevskaya, I.; Monia, B. P.; Holmlund, J.; Dorr, F. A.; Yao, K. S. c-raf-1 Depletion and Tumor Responses in Patients treated with the c-raf-1 Antisense Oligodeoxynucleotide ISIS 5132 (CGP 69846A). Clin. Cancer Res. 1999, 5, 3977-3982.
19. Stevenson, J. P.; Yao, K. S.; Gallagher, M.; Friedland, D.; Mitchell, E. P.; Cassella, A.; Monia, B.; Kwoh, T. J.; Yu, R.; Holmlund, J.; Dorr, F. A.; O'Dwyer, P. J. Phase I Clinical/pharmacokinetic and Pharmacodynamic Trial of the c-raf-1 Antisense Oligonucleotide ISIS 5132 (CGP 69846A). J. Clin. Oncol. 1999, 17, 2227-2236.
20. deFabritiis, P.; Calabretta, B. Antisense Oligodeoxynucleotides for the Treatment of Chronic Myelogenous Leukemia: are They Still a Promise? Haematologica 1995, 80, 295-299.
21. Bishop, M. R.; Jackson, J. D.; Tarantolo, S. R.; O'KaneMurphy, B.; Iversen, P. L.; Bayever, E.; Joshi, S. M.; Sharp, J. G.; Pierson, J. L.; Warkentin, P. I.; Armitage, J. O.; Kessinger, A. Ex vivo treatment of Bone Marrow with Phosphorothioate Oligonucleotide OL(l)p53 for Autologous Transplantation in Acute Myelogenous Leukemia and Myelodysplastic Syndrome. J. Hematother. 1997, 6, 441-446.
22. Bishop, M. R.; Iversen, P. L.; Bayever, E.; Sharp, J. G.; Greiner, T. C.; Copple, B. L.; Ruddon, R.; Zon, G.; Spinolo, J.; Arneson, M.; Armitage, J. O.; Kessinger, A. Phase I Trial of an Antisense Oligonucleotide OL(l)p53 in Hématologie Malignancies. J. Clin. Oncol. 1996, 14, 1320-1326.
23. Nemunaitis, J.; Holmlund, J. T.; Kraynak, M.; Richards, D.; Bruce, J.; Ognoskie, N.; Kwoh, T. J.; Geary, R.; Dorr, A.; Von Hoff, D.; Eckhardt, S. G. Phase I evaluation of ISIS 3521, an antisense Oligodeoxynucleotide to protein kinase C-alpha, in patients with advanced cancer. J. Clin. Oncol. 1999, 17, 3586-3595.
24. Yuen, A. R.; Halsey, J.; Fisher, G. A.; Holmlund, J. T.; Geary, R. S.; Kwoh, T. J.; Dorr, A.; Sikic, B. I. Phase I Study of an Antisense Oligonucleotide to Protein Kinase C-alpha (ISIS 3521/CGP 64128A) in Patients with Cancer. Clin. Cancer Res. 1999, 5, 3357-3363.
25. Wright, J. A.; Feng, N. P., Jin, H. N.; Wang, M.; Lee, Y.; Young, A. GTI-2040, an Outstanding Antisense Antitumor Agent that Targets the R2 Component of Human Ribonucleotide Reductase: From the Laboratory to the Clinic. Proc. Am. Assoc. Cancer Res. 2001, 42, Abs. 4559.
26. Wright, J. A.; Feng, N. P., Jin, H. N.; Wang, M.; Lee, Y.; Young,. A. GTI-2501, an Outstanding Antisense Antitumor Agent that Targets the Rl Component of Human Ribonucleotide Reductase. Proc. Am. Assoc. Cancer Res. 2001, 42, Abs. 4560.
27. Andrews, D. W.; Resnicoff, M.; Flanders, A. E.; Kenyon, L.; Curtis, M.; Merli, G.; Baserga, R.; Iliakis, G.; Aiken, R. D. Results of a Pilot study Involving the Use of an Antisense Oligodeoxynucleotide Directed against the Insulin-Like Growth Factor Type I Receptor in Malignant Astrocytomas. J. Clin. Oncol.2001,19, 2189-2200.
28. Ciardiello, F.; Caputo, R.; Troiani, T.; Borriello, G.; Kandimalla, E. R.; Agrawal, S.; Mendelsohn, J.; Bianco, A. R.; Tortora, G. Antisense Oligonucleotides Targeting the Epidermal Growth Factor Receptor Inhibit Proliferation, Induce Apoptosis, and Cooperate with Cytotoxic Drugs in Human Cancer Cell Lines. Int. J. Cancer 2001, 93, 172-178.
29. Wang H, Zeng X, Oliver P, Le LP, Chen J, Chen L, Zhou W, Agrawal S, Zhang R. MDM2 Oncogene as a Target for Cancer Therapy: An Antisense Approach. Int. J. Oncol. 1999,15, 653-660.
30. Chen L, Agrawal S, Zhou W, Zhang R, Chen J. Synergistic Activation of p53 by Inhibition of MDM2 Expression and DNA Damage. Proc. Natl. Acad. Sei. USA 1998, 95, 195-200.
31. Tortora, G.; Caputo, R.; Damiano, V.; Bianco, R.; Chen, J.; Agrawal, S.; Bianco, A. R.; Ciardiello, F. A Novel MDM2 Anti-Sense Oligonucleotide Has Anti-Tumor Activity and Potentiates Cytotoxic Drugs Acting by Different Mechanisms in Human Colon Cancer. //;J. J. ' Cancer 2000, 88, 804-809.
32. Tortora, G.; Caputo, R.; Damiano, V.; Bianco, R.; Pepe, S.; Pomatico, G.; Bianco, A. R.; Jiang, Z.; Agrawal, S.; Ciardiello, F. Cooperative Antitumor Effect of Mixed backbone Oligonucleotides Targeting Protein Kinase A in Combination with Cytotoxic Drugs or Biologic Agents. Antisense Nucleic Acid Drug Dev. 1998, 5,141-145.
33. Tortora, G.; Caputo, R.; Damiano, V.; Bianco, R.; Pepe, S.; Bianco, A, R.; Jiang, Z.; Agrawal, S.; Ciardiello, F. Synergistic Inhibition of Human Cancer Cell Growth by Cytotoxic Drugs and Mixed Backbone Antisense Oligonucleotide Targeting Protein Kinase A. Proc. Natl. Acad. Sei. USA 1997,94, 12586-12591.
34. Tortora, G.; Caputo, R.; Pomatico, G.; Pepe, S.; Bianco, A. R.; Agrawal, S.; Mendelsohn, J.; Ciardiello, F. Cooperative Inhibitory Effect of Novel Mixed Backbone Oligonucleotide Targeting Protein Kinase A in Combination with Docetaxel and Anti-Epidermal Growth Factor-Receptor Antibody on Human Breast Cancer Cell Growth. Clin. Cancer Res. 1999, 5, 875-881.
35. Wang, H.; Cai, Q.; Zeng, X.; Yu, D.; Agrawal, S.; Zhang, R. Antitumor Activity and Pharmacokinetics of a Mixedbackbone Antisense Oligonucleotide Targeted to the RIalpha Subunit of Protein Kinase A after' Oral Administration. Proc. Natl. Acad. Sei. USA 1999, 96, 13989-13994.
36. Akie, K.; Dosaka-Akita, H.; Murakami, A.; Kawakami, Y. A Combination Treatment of C-myc Antisense DNA with All-Trans-Retinoic Acid Inhibits Cell Proliferation by Downregulating C-myc Expression in Small Cell Lung Cancer. Antisense Nucleic Acid Drug Dev. 2000, 10, 243-249.
37. Geiger, T.; Muller, M.; Dean, N. M.; Fabbro, D. Antitumor Activity of a PKC-alpha Antisense Oligonucleotide in Combination with Standard Chemotherapeutic Agents against Various Human Tumors Transplanted into Nude Mice. Anticancer Drug Des. 1998, 13, 35-45.
38. Lopes de Menezes, D. E.; Hudon, N.; Mclntosh, N.; Mayer, L. D. Molecular and Pharmacokinetic Properties Associated with the Therapeutics of bcl-2 Antisense Oligonucleotide G3139 Combined with Free and Liposomal Doxorubicin. Clin. Cancer Res. 2000, 6, 2891-2902.
39. Wang, M. B.; Yip, H. T.; Srivatsan, E. S. Antisense Cyclin Dl Enhances Sensitivity of Head and Neck Cancer Cells to Cisplatin. Laryngoscope 2001, 111, 982-988.
40. Agrawal, S.; Kandimalla, E. R.; Yu, D.; Hollister, B. A.; Chen, S. F.; Dexter, D. L.; Alford, T. L.; Hill, B.; Bailey, K. S.; Bono, C. P.; Knoerzer, D. L.; Morton, P. A. Potentiation of Antitumor Activity of Irinotecan by Chemically Modified Oligonucleotides. Int. J. Oucol. 2001, 18, 1061-1069.
41. Jansen, B.; Wacheck, V.; Heere-Ress, E.; Schlagbauer-Wadl, H.; Hoeller, C.; Lucas, T.; Hoermann, M.; Hollenstein, U.; Wolff, K.; Pehamberger, H. Chemosensitisation of Malignant Melanoma by BCL2 Antisense Therapy. Lancet 2000, 356, 1728-1733.
42. Agrawal, S.; Rustagi, P. K.; Shaw, D. R. Novel Enzymatic and Immunological Responses to Oligonucleotides. Toxicol. Lett. 1995,82-83, 431-434.
43. Agrawal, S.; Zhao, Q.; Jiang, Z.; Oliver, C.; Giles, H.; Heath, J.; Serota, D. Toxicologie Effects of an Oligodeoxynucleotide Phosphorothioate and Its Analogs Following Intravenous Administration in Rats. Antisense Nucleic Acid Drug Dev. 1997, 7, 575-584.
44. Henry, S. P.; Zuckerman, J. E.; Rojko, J.; Hall, W. C.; Harman, R. J.; Kitchen, D.; Crooke, S. T. Toxicological Properties of Several Novel Oligonucleotide Analogs in Mice. Anticancer Drug Des. 1997, 12, 1-14.
45. Galbraith, W. M.; Hobson, W. C.; Giclas, P. C.; Schlechter, P. J.; Agrawal, S. Complement Activation and Hemodynamic Changes Following Intravenous Administration of Phosphorothioate Oligonucleotides in the Monkey. Antisense Res. Dev. 1994, 4, 201-206.
46. Scheeler, P. J.; Martin, R. R. In Antisense Research and Applications; Crooke, S. T., Ed.; Springer: New York, 1998, pp. 233-241.
47. Agrawal, S.; Zhao, Q. Mixed Backbone Oligonucleotides: Improvement in OligonucleotideInduced Toxicity in Vivo. Antisense Nucleic Acid Drug Dev. 1998, 8, 135-139.
48. Agrawal, S.; ladarola, P. L.; Temsamani, J.; Zhao, Q.; Shaw, D. R. Effect of G-Rich Sequences on the Synthesis, Purification, Binding, Cell Uptake, and Hemolytic Activity of Oligonucleotides. Bioorg. Med. Chem. Letts. 1996,6,2219-2224.
49. Agrawal, S.; Kandimalla, E. R. Antisense Therapeutics: Is It as Simple as Complementary Base Recognition? Mol. Med. Today 2000, 6, 72-81.
50. Matsukura, M.; Zon, G.; Shinozuka, K.; Robert-Guroff, M.; Shimada, T.; Stein, C. A.; Mitsuya, H.; Wong-Staal, F.; Cohen, J. S.; Border, S. Regulation of Viral Expression of Human Immunodeficiency Virus In Vitro by an Antisense Phosphorothioate Oligodeoxynucleotide Against rev (art/trs) in Chronically Infected Cells. Proc. Natl. Acad. Sei. USA 1989, 85, 7079-7083.
51. Branda, R. F.; Moore, A. L.; Mathews, L.; McCormack, J. J.; Zon, G. Immune Stimulation by an Antisense Oligomer Complementary to the Rev Gene of HIV-1. Biochem. Pharmacol. 1993, 45, 2037-2043.
52. Zhao, Q.; Temsamani, J.; ladarola, P. L.; Jiang, Z.; Agrawal, S. Effect of Different Chemically Modified Oligodeoxynucleotides on Immune Stimulation. Biochem. Pharmacol. 1996, 51, 173-182.
53. Shaw, D. R.; Rustagi, P. K.; Kandimalla, E. R.; Manning, A. N.; Jiang, Z.; Agrawal, S. Effects of Synthetic Oligonucleotides on Human Complement and Coagulation. Biochem. Pharmacol. 1997, 53, 1123-1132.
54. Kandimalla, E. R.; Shaw DR.; Agrawal S. Effects of Phosphorothioate Oligodeoxyribonucleotide and Oligoribonucleotides on Human Complement and Coagulation. Bioorg. Med. Chem. Lett. 1998, A, 2103-2108.
55. Agrawal, S.; Jiang, Z.; Zhao, Q.; Shaw, D.; Cai, Q.; Roskey, A.; Channavajjala, L.; Saxinger, C.; Zhang, R. Mixed-Backbone Oligonucleotides as Second Generation Antisense Oligonucleotides: In Vitro and In Vivo Studies. Proc. Natl. Acad Sei. USA 1997, 94, 2620-2625.
56. Kandimalla, E. R.; Manning, A.; Zhao, Q.; Shaw, D. R.; Byrn, R. A.; Sasisekharan, V.; Agrawal, S. Mixed Backbone Antisense Oligonucleotides: Design, Biochemical and Biological Properties of Oligonucleotides Containing 2′-5′-Ribo- and 3′-5′-Deoxyribonucleotide Segments. Nucleic Acids Res. 1997, 25, 370-378.
57. Zhou, W.; Agrawal, S. Mixed-Backbone Oligonucleotides as Second-Generation Antisense Agents with Reduced Phosphorothioate-Related Side Effects. Bioorg. Med Chem. Lett. 1998, 8, 3269-3274.
58. Chen, H. X.; Marshall, J. L.; Ness, E.; Martin, R. R.; Dvorchik, B.; Rizvi, N.; Marquis, J.; McKinlay, M.; Dahut, W.; Hawkins, M. J. A Safety and Pharmacokinetic Study of a Mixed-Backbone Oligonucleotide (GEM231) Targeting the Type I Protein Kinase A by Two-Hour Infusions in Patients with Refractory Solid Tumors. Clin. Cancer Res. 2000, 6, 1259-1266.
59. Lewis, E. J.; Agrawal, S.; Bishop, J.; Chadwick, J.; Cristensen, N. D.; Cuthill, S.; Dunford, P.; Field, A. K.; Francis, J.; Gibson ,V.; Greenham, A. K.; Kelly; F.; Kilkushie, R.; Kreider, J. W.; Mills, J. S.; Mulqueen, M.; Roberts, N..A.; Roberts, P.; Szymkowski, D. E. NonSpecific Antiviral Activity of Antisense Molecules Targeted to the El Region of Human Papillomavirus. Antiviral Res. 2000, 48, 187-196.
60. Klinman, D. M.; Yi, A. K.; Beaucage, S. L.; Conover, J.; Krieg, A. M. CpG Motifs Present in Bacteria DNA Rapidly induce Lymphocytes to Secrete Interleukin 6, Interleukin 12, and Interferon Gamma. Proc. Natl. Acad. Sei. USA 1996, 93, 2879-2883.
61. Zhao Q.; Temsamani J.; Zhou, R. Z.; Agrawal S. Pattern and Kinetics of Cytokine Production Following Administration of Phosphorothioate Oligonucleotides in Mice. Antisense Nucleic Acid Drug Dev. 1997, 7, 495-502.
62. Dutcher, J. P. Therapeutic Strategies for Cytokines. Curr. Opin. Oncol. 1995, 7, 566-571.
63. Salgaller, M. L.; Lodge, P. A. Use of Cellular and Cytokine Adjuvants in the Immunotherapy of Cancer. J. Surg. Oncol. 1998, 68, 122-138.
64. Hiscox, S.; Jiang, W. G. Interleukin-12, an Emerging Anti-Tumour Cytokine. In Vivo 1997, 11, 125-132.
65. Yamamoto, S.; Kuramoto, E.; Shimada, S.; Tokunaga, T. In Vitro Augmentation of Natural Killer Cell Activity and Production of Interferon-Alpha/Beta and-Gamma with Deoxyribonucleic Acid Fraction from Mycobacterium Bovis BCG. Jpn. J. Cancer Res. 1988, 79, 866-873.
66. Messina, J. P.; Gilkeson, G. S.; Pisetsky, D. S. Stimulation of in Vitro Murine Lymphocyte Proliferation by Bacterial DNA. J. Immunol. 1991,147, 1759-1764.
67. Krieg, A. M.; Yi, A. K.; Maison, S.; Waldschmidt, T. J.; Bishop, G. A.; Teasdale, R.; Koretzky, G. A.; Klinman, D. M. CpG Motifs in Bacterial DNA Trigger Direct B-Cell Activation. Nature 1995, 374, 546-549.
68. Hartmann, G.; Weeratna, R. D.; Ballas, Z. K.; Fayette, P.; Blackwell, S.; Suparto, I.; Rasmussen, W. L.; Waldschmidt, M.; Sajuthi, D.; Purcell, R. H.; Davis, H. L.; Krieg, A. M. Delineation of a CpG Phosphorothioate Oligodeoxynucleotide for Activating Primate Immune Responses in Vitro and in Vivo. J. Immunol. 2000,164, 1617-1624.
69. Verthelyi, D.; Ishii, K. J.; Gursel, M.; Takeshita, F.; Klinman, D. M. Human Peripheral Blood Cells Differentially Recognize and Respond to Two Distinct CpG Motifs. J. Immunol. 2001, 166, 2372-2377.
70. Hafner, M.; Zawatzky, R.; Hirtreiter, C.; Buurman, W. A.; Echtenacher, B.; Hehlgans, T.; Mannel, D. N. Antimetastatic Effect of CpG DNA Mediated by Type I IFN. Cancer Res. 2001, 61, 5523-8552.
71. Chen, W.; Yu, Y.; Shao, C.; Zhang, M.; Wang, W.; Zhang, L.; Cao, X. Enhancement of Antigen-Presenting Ability of B Lymphoma Cells by Immunostimulatory CpG-Oligonucleotides and Anti-CD40 Antibody. Immunol. Lett. 2000, 77, 17-2.
72. Jahrsdorfer, B.; Hartmann, G.; Racila, E.; Jackson, W.; Muhlenhoff, L.; Meinhardt, G.; Endres, S.; Link, B. K.; Krieg, A. M.; Weiner, G. J. CpG DNA Increases Primary Malignant B Cell Expression of Costimulatory Molecules and Target Antigens. J. Leukoc. Biol. 2001, 69, 81-88.
73. Brunner, C.; Seiderer, J.; Schlamp, A.; Bidlingmaier, M.; Eigler, A.; HaimerI, W.; Lehr, H. A.; Krieg, A. M.; Hartmann, G.; Endres, S. Enhanced Dendritic Cell Maturation by TNF-Alpha or Cytidine-PhosphateGuanosine DNA Drives T Cell Activation in Vitro and Therapeutic Anti-Tumor Immune Responses in Vivo. J. Immunol. 2000, 765, 6278-6286.
74. Kim, S. K.; Ragupathi, G.; Cappello, S.; Kagan, E.; Livingston, P. O. Effect of Immunological Adjuvant Combinations on the Antibody and T-cell Response to Vaccination with MUCl-KLH and GD3-KLH Conjugates. Vaccine 2000, 19, 530-537.
75. Yamamoto, S.; Yamamoto, T.; Iho, S.; Tokunaga, T. Activation of NK Cell (Human and Mouse) by Immunostimulatory DNA Sequence. Springer Semin. Immunopathol. 2000, 22, 35-43.
76. Cafaro, A.; Titti, F.; Fracasso, C.; Maggiorella, M. T.; Baroncelli, S.; Caputo, A.; Goletti, D.; Borsetti, A.; Pace, M.; Fanales-Belasio, E.; Ridolfi, B.; Negri, D. R.; Sernicola, L.; Belli, R.; Corrias, F.; Macchia, I.; Leone, P.; Michelini, Z.; ten Haaft, P.; Butto, S.; Verani, P.; Ensoli, B. Vaccination with DNA Containing Tat Coding Sequences and Unmethylated CpG Motifs Protects Cynomolgus Monkeys upon Infection with Simian/Human Immunodeficiency Virus (SHIV89.6P). Vaccine200l, 19, 2862-2877.
77. Gallichan, W. S.; Woolstencroft, R. N.; Guarasci, T.; McCluskie, M. J.; Davis, H. L.; Rosenthal, K. L. Intranasal Immunization with CpG Oligodeoxynucleotides as an Adjuvant Dramatically Increases IgA and Protection against Herpes Simplex Virus-2 in the Genital Tract. J. Immunol.2001, 166, 3451-3457.
78. Tighe, H.; Takabayashi, K.; Schwartz, D.; Van Nest, G.; Tuck, S.; Eiden, J. J.; Kagey-Sobotka, A.; Creticos, P. S.; Lichtenstein, L. M.; Spiegelberg, H. L.; Raz, E. Conjugation of Immunostimulatory DNA to the Short Ragweed Allergen Amb a 1 Enhances Its Immunogenicity and Reduces Its Allergenicity. J. Allergy Clin. Immunol. 2000, 106, 124-134.
79. Davis, H. L.; Suparto, I. I.; Weeratna, R. R.; Jumintarto.; Iskandriati, D. D.; Chamzah, S. S.; Ma'ruf, A. A.; Nente, C. C.; Pawitri, D. D.; Krieg, A. M.; Heriyanto.; Smits, W.; Sajuthi, D. D. CpG DNA Overcomes Hyporesponsiveness to Hepatitis B Vaccine in Orangutans. Vaccine 2000, 18, 1920-1924.
80. Jones, T. R.; Obaldia, N. 3rd.; Gramzinski, R. A.; Charoenvit, Y.; Kolodny, N.; Kitov, S.; Davis, H. L.; Krieg, A. M.; Hoffman, S. L. Synthetic Oligodeoxynucleotides Containing CpG Motifs Enhance Immunogenicity of a Peptide Malaria Vaccine in Aotus Monkeys. Vaccine 1999, 17, 3065-3071.
81. Oxenius, A.; Martinic, M. M.; Hengartner, H.; Klenerman, P. CpG-Containing Oligonucleotides are Efficient Adjuvants for Induction of Protective Antiviral Immune Responses with T-Cell Peptide Vaccines. J. Virol. 1999, 73, 4120-4126.
82. Zhang, R.; Lu, Z.; Zhao, H.; Zhang, X.; Diasio, R. B.; Habus, I.; Jiang, Z.; lyer, R. P.; Yu, D.; Agrawal, S. In Vivo Stability, Disposition and Metabolism of a "Hybrid" Oligonucleotide Phosphorothioate in Rats. Biochem. Pharmacol. 1995,50, 545-556.
83. Zhao Q.; Yu D.; Agrawal S. Site of Chemical Modifications in CpG Containing Phosphorothioate Oligodeoxynucleotide Modulates Its Immunostimulatory Activity. Bioorg. Meet. Chem. Lett. 1999, 9, 3453-3458.
84. Zhao Q.; Yu D.; Agrawal S. Immunostimulatory Activity of CpG Containing Phosphorothioate Oligodeoxynucleotide is Modulated by Modification of a Single Deoxynucleoside. Bioorg. Med. Chem. Lett. 2000,70, 1051-1054.
85. Yu, D.; Kandimalia, E. R.; Zhao, Q.; Cong, Y.; Agrawal, S. Immunostimulatory Activity of CpG Oligonucleotides Containing Non-Ionic Methylphosphonate Linkages. Bioorg. Med Chem. 2001,9, 2803-2808.
86. Yu, D.; Kandimalia, E. R.; Zhao, Q.; Cong, Y.; Agrawal, S. Modulation of Immunostimulatory Activity of CpG Oligonucleotides by Site-Specific Deletion of Nucleobases. Bioorg. Med. Chem. Lett. 2001,11, 2263- 2267. .
87. Kandimalia, E. R.; Yu, D.; Zhao, Q.; Agrawal, S. Effect of Chemical Modifications of Cytosine and Guanine in a CpG-Motif of Oligonucleotides: Structure-Immunostimulatory Activity Relationships. Bioorg. Med. Chem. 2001, 9, 807-813.
88. Yu, D.; Zhao, Q.; Kandimalia, E. R.; Agrawal, S. Accessible 5'-End of CpG-Containing Phosphorothioate Oligodeoxynucleotides is Essential for Immunostimulatory Activity. Bioorg. Med. Chem. Lett. 2000, 10, 2585-2588.
89. Hemmi, H.; Takeuchi, O.; Kawai, T.; Kaisho, T.; Sato, S.; Sanjo, H.; Matsumoto, M.; Hoshino, K.; Wagner, H.; Takeda, K.; Akira, S. A Toll-Like Receptor recognizes Bacterial DNA. Nature 2000, 408, 740-745.
90. Chu, W.; Gong, X.; Li, Z.; Takabayashi, K.; Ouyang, H.; Chen, Y.; Lois, A.; Chen, D. J.; Li, G. C.; Karin, M.; Raz, E. DNA-PKcs is Required for Activation of Innate Immunity by Immunostimulatory DNA. Cell 2000, 103, 909-918.
91. Stephenson, M. L.; Zamecnik, P. C. Inhibition of Rous Sarcoma Viral RNA Translation by ' a Specific Oligodeoxyribonucleotide. Proc. Natl. Acad. Sei. USA 1978, 75, 285-288.
92. Zamecnik, P. C.; Stephenson, M. L. Inhibition of Rous Sarcoma Virus Replication and Cell Transformation by a Specific Oligodeoxynucleotide. Proc. Natl. Acad. Sei. USA 1978, 75, 280-284.
93. Agrawal, S.; Zhang, X.; Lu, Z.; Zhao, H.; Tamburin, J. M.; Yan, J.; Cai, H.; Diasio, R. B.; Habus I, Jiang Z, lyer, R. P.; Yu, D.; Zhang, R. Absorption, Tissue Distribution and in Vivo Stability in Rats of a Hybrid Antisense Oligonucleotide Following Oral Administration. Biochem. Pharmacol. 1995,50, 571-576.