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Immune System
ISS
IRS
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Technology :: Publications

General | HEPLISAV | Influenza | Allergy/ Asthma | IRS / TLR Inhibitors | ISS / TLR | Cancer

General

Ahmed SS, Plotkin SA, Black S, Coffman RL. Assessing the safety of adjuvanted vaccines. Sci. Transl. Med., 2011; 3(93):93rv2.

Coffman, RL, Sher A, Seder RA.  Vaccine adjuvants: putting innate immunity to work. Immunity, 2010; 33(4):492-503.

Frank J. Barrat and Robert L. Coffman. Development of TLR inhibitors for the treatment of autoimmune diseases. Immunological Reviews, 2008; 223:271-283.

Debbie Higgins, Jason D Marshal, Paula Traquina, Gary Van Nest and Brian Livingston. Immunostimulatory DNA as a Vaccine Adjuvant. The Expert Review of Vaccines, 2007; 6(5):747-759.

Holger Kanzler, Franck J Barrat, Edith M Hessel & Robert L Coffman. Therapeutic targeting of innate immunity with Toll-like receptor agonists and antagonists. Nature Medicine, 2007; 13(5):552-559.

Robert L. Coffman. Origins of the Th1-Th2 model: a personal perspective. Nat. Immunol., 2006; 7(6):539-41.

Tomoko Hayashi, MD, PhD, Eyal Raz, MD. TLR9-Based Immunotherapy for Allergic Disease. The American Journal of Medicine, 2006; 119(10):897.e1-6

Livingston BD, Higgins D, Van Nest G. Evolving strategies for the prevention of influenza infection: potential for multistrain targeting. BioDrugs, 2006; 20(6):335-340.

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HEPLISAV

Scott A. Halperin, Shelly McNeil, Joanne M. Langley, Bruce Smith, Donna MacKinnon-Cameron, Robyn McCall-Sani, William L. Heyward, J. Tyler Martin. Safety and immunogenicity of different two-dose regimens of an investigational hepatitis B vaccine (hepatitis B surface antigen co-administered with an immunostimulatory phosphorothioate oligodeoxyribonucleotide) in healthy young adults. Vaccine, 2012; 30(36):5445-5448.  

Benjamin P. Sablan, Dong Joon Kim, Nina G. Barzaga, Wan Cheng Chow, Mong Cho, Sang Hoon Ahn, Seong Gyu Hwang, Ji Hyun Lee, Hamid Namini, William L. Heyward. Demonstration of safety and enhanced seroprotection against hepatitis B with investigational HBsAg-1018 ISS vaccine compared to a licensed hepatitis B vaccine. Vaccine, 2012; 30(16): 2689-2696.

Scott A. Halperin, Brian Ward, Curtis Cooper, Gerald Predy, Francisco Diaz-Mitoma, Marc Dionne, Joanne Embree, Allison McGeer, Paul Zickler, Karl-Heinz Moltz, René Martz, Ingo Meyer, Shelly McNeil, Joanne M. Langley, Eduardo Martins, William L. Heyward, J. Tyler Martin. Comparison of safety and immunogenicity of two doses of investigational hepatitis B virus surface antigen co-administered with an immunostimulatory phosphorothioate oligodeoxyribonucleotide and three doses of a licensed hepatitis B vaccine in healthy adults 18–55 years of age. Vaccine, 2012; 30(15): 2556-2563.

Scott A. Halperin, Simon Dobson, Shelly McNeil, Joanne M. Langley, Bruce Smith, Robyn McCall-Sani, Dan Levitt, Gary Van Nest, Daniel Gennevois, Joseph J. Eiden. Comparison of the safety and immunogenicity of hepatitis B virus surface antigen co-administered with an immunostimulatory phosphorothioate oligonucleotide and a licensed hepatitis B vaccine in healthy young adults. Vaccine, 2006; 24(1): 20-26.

Halperin, S.A., G. Van Nest, B. Smith, S. Abtahi, H. Whiley, and J.J. Eiden. A phase I study of the safety and immunogenicity of recombinant hepatitis B surface antigen co-administered with an immunostimulatory phosphorothioate oligonucleotide adjuvant. Vaccine, 2003; 21(19-20): 2461-2467.

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Influenza

Livingston BD, Higgins D, Van Nest G. Evolving strategies for the prevention of influenza infection: potential for multistrain targeting. BioDrugs, 2006; 6(20):335-340(6).

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Allergy / Asthma

Campbell JD, Buchmann P, Kesting S, Cunningham CR, Coffman RL, Hessel EM. Allergen-specific T cell responses to immunotherapy monitored by CD154 and intracellular cytokine expression. Clin. Exp. Allergy, 2010; 40(7):1025-35.

John D. Campbell, Yan Cho, Martyn L. Foster, Holger Kanzler, Melissa A. Kachura, Jeremy A. Lum, Marianne J. Ratcliffe, Atul Sathe, Andrew J. Leishman, Ash Bahl, Mark McHale, Robert L. Coffman and Edith M. Hessel. CpG-containing immunostimulatory DNA sequences elicit TNF-α–dependent toxicity in rodents but not in humans: J. Clin. Invest., 2009; 119(9):2564–2576.

Tomoko Hayashi, MD, PhD, Eyal Raz, MD. TLR9-Based Immunotherapy for Allergic Disease. The American Journal of Medicine, 2006; 119(10):897.e1-6.

Peter S. Creticos, M.D., John T. Schroeder, Ph.D., Robert G. Hamilton, Ph.D., Susan L. Balcer-Whaley, M.P.H., Arouna P. Khattignavong, M.D., Robert Lindblad, M.D., Henry Li, M.D., Ph.D., Robert Coffman, Ph.D., Vicki Seyfert, Ph.D., Joseph J. Eiden, M.D., Ph.D., David Broide, M.B., Ch.B., and the Immune Tolerance Network Group. Immunotherapy with a ragweed-toll-like receptor 9 agonist vaccine for allergic rhinitis. N. Engl. J. Med., 2006; 355(14):1445-55.

Higgins, D., Rodriguez, R., Milley, R., Marshall, J., Abbate, C., dela Cruz, T., Patton, K., Walker, F., Chichester, K., Eiden, J., Tuck, S., Van Nest, G. Modulation of immunogenicity and allergenicity by controlling the number of immunostimulatory oligonucleotides linked to Amb a 1. J. Allergy and Clin. Immunol., 2006; 118(2):504-10.

Robert L. Coffman. Origins of the Th1-Th2 model: a personal perspective. Nat. Immunol., 2006; 7(6):539-41.

Gail M Gauvreau, Edith M Hessel, Louis-Philippe Boulet, Robert L Coffman, and Paul M O'Byrne. Immunostimulatory Sequences Regulate Interferon-inducible Genes but not Allergic Airway Responses. Am. J. Respir. Crit. Care Med., 2006; 174(1):15-20.

Edith M. Hessel, Mabel Chu, Jennifer O. Lizcano, Bonnie Chang, Nancy Herman, Sariah A. Kell, Marsha Willis-Karp, and Robert L. Coffman. Immunostimulatory oligonucleotides block allergic airway inflammation by inhibiting Th2 cell activation and IgE-mediated cytokine induction. J. Exp. Med., 2005; 202(11):1563-1573. View in PDF Format.

Robert L. Coffman and Edith M. Hessel. Nonhuman primate models of asthma.  J. Exp. Med., 2005; 201(12):1875–1879.  View in PDF Format.

Simons, F.E., Y. Shikishima, G. Van Nest, J.J. Eiden, and K.T. HayGlass. Selective immune redirection in humans with ragweed allergy by injecting Amb a 1 linked to immunostimulatory DNA. J. Allergy Clin. Immunol., 2004; 113(6):1144-1151.

Tulic, M.K., P.O. Fiset, P. Christodoulopoulos, P. Vaillancourt, M. Desrosiers, F. Lavigne, J. Eiden, and Q. Hamid. Amb a 1-immunostimulatory oligodeoxynucleotide conjugate immunotherapy decreases the nasal inflammatory response. J. Allergy Clin. Immunol., 2004; 113(2):235-241.

Santeliz, J.V., G. Van Nest, P. Traquina, E. Larsen, and M. Wills-Karp. Amb a 1-linked CpG Oligodeoxynucleotides Reverse Established Airway Hyperresponsiveness in a Murine Model of Asthma. J. Allergy Clin. Immunol., 2002; 109:455-462.

Marshall, J.D., S. Abtahi, J.J. Eiden, S. Tuck, R. Milley, F. Haycock, M.J. Reid, A. Kagey-Sobotka, P.S. Creticos, L.M. Lichtenstein, and G. Van Nest. Immunostimulatory Sequence DNA Linked to the Amb a 1 Allergen Promotes Th1 Cytokine Expression While Downregulating Th2 Cytokine Expression in PBMCs from Human Patients with Ragweed Allergy. J. Allergy Clin. Immunol., 2001; 108:191-197.

Tighe, H., K. Takabayashi, D. Schwartz, G. Van Nest, S. Tuck, J.J. Eiden, A. Kagey-Sobotka, P.S. Creticos, L.M. Lichtenstein, H.L. Spiegelberg, and E. Raz. 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.

Van Uden, J. and E. Raz. Immunostimulatory DNA and Applications to Allergic Disease. J. Allergy Clin. Immunol., 1999; 104:902-910.

Broide, D., J. Schwarze, H. Tighe, T. Gifford, M.D. Nguyen, S. Malek, J. Van Uden, E. Martin-Orozco, E.W. Gelfand, and E. Raz. Immunostimulatory DNA Sequences Inhibit IL-5, Eosinophilic Inflammation, and Airway Hyperresponsiveness in Mice. J. Immunol., 1998; 161:7054-7062.

Spiegelberg, H.L., E.M. Orozco, M. Roman, and E. Raz. DNA Immunization: A Novel Approach to Allergen-specific Immunotherapy. Allergy, 1997; 52:964-970.

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IRS / TLR Inhibitors

Garcia-Romo GS, Caielli S, Vega B, Connolly J, Allantaz F, Xu Z, Punaro M, Baisch J, Guiducci C, Coffman RL, Barrat FJ, Banchereau J, Pascual V. Netting neutrophils are major inducers of type I IFN production in pediatric systemic lupus erythematosus. Sci. Transl. Med., 2011; 3(73):73ra20. PMCID: 3143837.

Guiducci C, Tripodo C, Gong M, Sangaletti S, Colombo MP, Coffman RL, Barrat FJ. Autoimmune skin inflammation is dependent on plasmacytoid dendritic cell activation by nucleic acids via TLR7 and TLR9. J. Exp. Med., 2010; 207(13):2931-42.

Guiducci C, Gong M, Xu Z, Gill M, Chaussabel D, Meeker T, Chan JH, Wright T, Punaro M, Bolland S, Soumelis V, Banchereau J, Coffman RL, Pascual V, Barrat FJ. TLR recognition of self nucleic acids hampers glucocorticoid activity in lupus. Nature, 2010; 465(7300):937-41.

Clancy RM, Alvarez D, Komissarova E, Barrat FJ, Swartz J, Buyon JP. Ro60-associated single-stranded RNA links inflammation with fetal cardiac fibrosis via ligation of TLRs: a novel pathway to autoimmune-associated heart block. J. Immunol., 2010; 184(4):2148-55.

D. Ganguly, G. Chamilos, R. Lande, J. Gregorio, S. Meller, V. Facchinetti, B. Homey, F.J. Barrat, T. Zal, and M. Gilliet. Self-RNA-antimicrobial peptide complexes activate human dendritic cells through TLR7 and TLR8. J. Exp. Med., 2009; 206(9):1983-94.

Guiducci C, Coffman RL, Barrat FJ (Dynavax Technologies Corporation, Berkeley, CA USA). Signalling pathways leading to IFN-a production in human PDC and the possible use of agonists or antagonists of TLR-7 and TLR-9 in clinical indications (Review). J. Intern. Med., 2008; 265:43-57.

Xiaoping Qing, Milena Pitashny, David B. Thomas, Franck J. Barrat, Mark P. Hogarth, Chaim Putterman. Pathogenic anti-DNA antibodies modulate gene expression in mesangial cells: Involvement of HMGB1 in anti-DNA antibody-induced renal injury. Immunology Letters, 2008; 121:61–73.

Frank J. Barrat and Robert L. Coffman. Development of TLR inhibitors for the treatment of autoimmune diseases. Immunological Reviews, 2008; 223:271-283.

Franck J. Barrat, Thea Meeker, Jean H. Chan, Cristiana Guiducci and Robert L. Coffman. Treatment of lupus-prone mice with a dual inhibitor of TLR7 and TLR9 leads to reduction of autoantibody production and amelioration of disease symptoms. Eur. J. Immunol., 2007; 37(12):3582-6.

Denny M.F., Thacker S., Mehta H., Somers E.C., Dodick T., Barrat F.J., McCune W.J. and Kaplan M.J.. Interferon-{alpha} promotes abnormal vasculogenesis in lupus: a potential pathway for premature atherosclerosis. Blood, 2007; 110:2907-2915.

Marshall JD, Heeke DS, Gesner ML, Livingston B, Van Nest G. Negative regulation of TLR9-mediated IFN-{alpha} induction by a small-molecule, synthetic TLR7 ligand. Journal of Leukocyte Biology, 2007; 82(3):497-508. View in PDF Format.

Holger Kanzler, Franck J Barrat, Edith M Hessel & Robert L Coffman. Therapeutic targeting of innate immunity with Toll-like receptor agonists and antagonists. Nature Medicine, 2007; 13(5):552 - 559.

Franck J. Barrat, Thea Meeker, Josh Gregorio, Jean H. Chan, Satoshi Uematsu, Shizuo Akira, Bonnie Chang, Omar Duramad, and Robert L. Coffman. Nucelic acids of mammalian origin can act as endogenous ligands for Toll-like receptors and may promote systemic lupus erythematosus. J. Exp. Med., 2005; 202(8):1131-1139. View in PDF Format.

Omar Duramad, Karen L. Fearon, Bonnie Chang, Jean H. Chan, Josh Gregorio, Robert L. Coffman, and Franck J. Barrat. Inhibitors of TLR-9 Act on Multiple Cell Subsets in Mouse and Man In Vitro and Prevent Death In Vivo from Systemic Inflammation. J. Immunol., 2005; 174:5193–5200. View in PDF Format.

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ISS / TLR

Hou B, Saudan P, Ott G, Wheeler ML, Ji M, Kuzmich L, Lee LM, Coffman RL, Bachmann MF, DeFranco AL. Selective utilization of Toll-like receptor and MyD88 signaling in B cells for enhancement of the antiviral germinal center response. Immunity, 2011; 34(3):375-384.

John D. Campbell, Yan Cho, Martyn L. Foster, Holger Kanzler, Melissa A. Kachura, Jeremy A. Lum, Marianne J. Ratcliffe, Atul Sathe, Andrew J. Leishman, Ash Bahl, Mark McHale, Robert L. Coffman and Edith M. Hessel. CpG-containing immunostimulatory DNA sequences elicit TNF-α–dependent toxicity in rodents but not in humans. J. Clin. Invest., 2009; 119(9):2564–2576.

Cristiana Guiducci, Cristina Ghirelli, Marie-Annick Marloie-Provost, Tracy Matray, Robert L. Coffman, Yong-Jun Liu, Franck J. Barrat, and Vassili Soumelis. PI3K is critical for the nuclear translocation of IRF-7 and type I IFN production by human plasmacytoid predendritic cells in response to TLR activation. J. Exp. Med., 2008; 205(2):315-22 View PDF File.

Holger Kanzler, Franck J Barrat, Edith M Hessel & Robert L Coffman. Therapeutic targeting of innate immunity with Toll-like receptor agonists and antagonists. Nature Medicine, 2007;13(5).

Felix Yarovinsky, Holger Kanzler, Sara Hieny, Robert L. Coffman, and Alan Sher. Toll-like Receptor Recognition Regulates Immunodominance in an Antimicrobial CD4+ T Cell Response. Immunity, 2006; 25:665-664.

Cristiana Guiducci, Gary Ott, Jean H. Chan, Emily Damon, Carlo Calacsan, Tracy Matray, Kyung-Dall Lee, Robert L. Coffman and Franck J. Barrat. Properties Regulating the Nature of the Plasmacytoid Dendritic Cell Response to TLR9 Activation. J. Exp. Med., 2006; 203(8):1999-2008. View in PDF Format

Jason D. Marshall, Darren S. Heeke, Christi Abbate, Priscilla Yee and Gary Van Nest. Induction of interferon-gamma from natural killer cells by immunostimulatory CpG DNA is mediated through plasmacytoid-dendritic-cell-produced interferon-alpha and tumor necrosis factor-alpha. Immunol., 2005; 117:38-46.

Kun Yang, Anne Puel, Shenying Zhang, Céline Eidenschenk, Cheng-Lung Ku, Armanda Casrouge, Capucine Picard, Horst von Bernuth, Brigitte Senechal, Sabine Plancoulaine, Sami Al-Hajjar, Abdulaziz Al-Ghonaium, László Maródi, Donald Davidson, David Speert, Chaim Roifman, Ben-Zion Garty, Adrian Ozinsky, Franck J. Barrat, Robert L. Coffman, Richard L. Miller, Xiaoxia Li, Pierre Lebon, Carlos Rodriguez-Gallego, Helen Chapel, Frédéric Geissmann, Emmanuelle Jouanguy, and Jean-Laurent Casanova. Human TLR-7-, -8-, and -9-Mediated Induction of IFN-alpha/beta and -lambda is IRAK-4 Dependent and Redundant for Protective Immunity to Viruses. Immunity, 2005; 23:465-478.

Marshall, J.D., K.L. Fearon, D. Higgins, E.M. Hessel, H. Kanzler, C. Abbate, P. Yee, J. Gregorio, T.D. Cruz, J.O. Lizcano, A. Zolotorev, H.M. McClure, K.M. Brasky, K.K. Murthy, R.L. Coffman, and G.V. Nest. Superior Activity of the Type C Class of ISS In Vitro and In Vivo Across Multiple Species. DNA Cell Biol., 2005; 24(2):63-72.

Marshall, J.D., D. Higgins, C. Abbate, P. Yee, G. Teshima, G. Ott, T. Dela Cruz, D. Passmore, K.L. Fearon, S. Tuck, and G. Van Nest. Polymyxin B enhances ISS-mediated immune responses across multiple species. Cell. Immunol., 2004; 229(2):93-105.

Teleshova, N., J. Kenney, J. Jones, J. Marshall, G. Van Nest, J. Dufour, R. Bohm, J.D. Lifson, A. Gettie, and M. Pope. CpG-C immunostimulatory oligodeoxyribonucleotide activation of plasmacytoid dendritic cells in rhesus macaques to augment the activation of IFN-gamma-secreting simian immunodeficiency virus-specific T cells. J. Immunol., 2004; 173(3):1647-1657.

Duramad, O., K.L. Fearon, J.H. Chan, H. Kanzler, J.D. Marshall, R.L. Coffman, and F.J. Barrat. IL-10 regulates plasmacytoid dendritic cell response to CpG-containing immunostimulatory sequences. Blood, 2003; 102(13):4487-4492.

Marshall, J.D., E.M. Hessel, J. Gregorio, C. Abbate, P. Yee, M. Chu, G.V. Nest, R.L. Coffman, and K.L. Fearon. Novel chimeric immunomodulatory compounds containing short CpG oligodeoxyribonucleotides have differential activities in human cells. Nucl. Acids Res., 2003; 31(17):5122-5133. View in PDF format.

Fearon, K., J.D. Marshall, C. Abbate, S. Subramanian, P. Yee, J. Gregorio, G. Teshima, G. Ott, S. Tuck, G. Van Nest, and R.L. Coffman. A minimal human immunostimulatory CpG motif that potently induces IFN-gamma and IFN-alpha production. Eur. J. Immunol., 2003; 33: 2114-2122.

Marshall, J.D., K. Fearon, C. Abbate, S. Subramanian, P. Yee, J. Gregorio, R.L. Coffman, and G. Van Nest. Identification of a novel CpG DNA class and motif that optimally stimulate B cell and plasmacytoid dendritic cell functions. J. Leukoc. Biol., 2003; 73(6):781-792.

Pyles, R.B., D. Higgins, C. Chalk, A. Zalar, J. Eiden, C. Brown, G. Van Nest, and L.R. Stanberry. Use of Immunostimulatory Sequence-Containing Oligonucleotides as Topical Therapy for Genital Herpes Simplex Virus Type 2 Infection. J. Virol., 2002; 76: 11387-11396. View in PDF format.

Horner, A.A., A. Ronaghy, P.M. Cheng, M.D. Nguyen, H.J. Cho, D. Broide, and E. Raz. Immunostimulatory DNA Is a Potent Mucosal Adjuvant. Cell. Immunol., 1998; 190: 77-82.

Roman, M., E. Martin-Orozco, J.S. Goodman, M.D. Nguyen, Y. Sato, A. Ronaghy, R.S. Kornbluth, D.D. Richman, D.A. Carson, and E. Raz. Immunostimulatory DNA Sequences Function as T helper-1-promoting Adjuvants. Nature Medicine, 1997; 3: 849-854.

Sato, Y., M. Roman, H. Tighe, D. Lee, M. Corr, M.D. Nguyen, G.J. Silverman, M. Lotz, D.A. Carson, and E. Raz. Immunostimulatory DNA Sequences Necessary for Effective Intradermal Gene Immunization. Science, 1996; 273: 352-354.

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Cancer

Friedberg JW, Kelly JL, Neuberg D, Peterson DR, Kutok JL, Salloum R, Brenn T, Fisher DC, Ronan E, Dalton V, Rich L, Marquis D, Sims P, Rothberg PG, Liesveld J, Fisher RI, Coffman R, Mosmann T, Freedman AS. Phase II study of a TLR-9 agonist (1018 ISS) with rituximab in patients with relapsed or refractory follicular lymphoma. Br J Haematol. 2009;146(3):282-91. PMCID: PMC2747261

Haining WN, Davies J, Kanzler H, Drury L, Brenn T, Evans J, Angelosanto J, Rivoli S, Russell K, George S, Sims P, Neuberg D, Li X, Kutok J, Morgan J, Wen P, Demetri G, Coffman RL, Nadler LM. CpG oligodeoxynucleotides alter lymphocyte and dendritic cell trafficking in humans. Clin Cancer Res. 2008;14(17):5626-34.

Friedberg, J.W., H. Kim, M. McCauley, E.M. Hessel, P. Sims, D.C. Fisher, L.M. Nadler, R.L. Coffman, and A.S. Freedman. Combination immunotherapy with a CpG oligonucleotide (1018 ISS) and rituximab in patients with non-Hodgkins lymphoma: increased interferon-alpha/beta-inducible gene expression, without significant toxicity. Blood, 2005. 105(2):489-495.

Cho, H.J., K. Takabayashi, P.M. Cheng, M.D. Nguyen, M. Corr, S. Tuck, and E. Raz. Immunostimulatory DNA-based Vaccines Induce Cytotoxic Lymphocyte Activity by a T Helper Cell-independent Mechanism. Nat. Biotechnol. 2000; 18: 509-514.

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