Prolonged subcutaneous administration of 852A, a novel systemic toll-like receptor 7 agonist, to activate innate immune responses in patients with advanced hematologic malignancies

American Journal of Hematology

Volumn 87, Issue 10, 2012, Pages 953-956

  Weigel, Brenda J ^a   Cooley, Sarah ^a   Defor, Todd ^a   Weisdorf, Daniel J ^a   Panoskaltsis Mortari, Angela ^a   Chen, Wei ^a   Blazar, Bruce R ^a   Miller, Jeffrey S ^a  

^a UNIVERSITY OF MINNESOTA MEDICAL SCHOOL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

N [4 (4 AMINO 2 ETHYL 1H IMIDAZO[4,5 C]QUINOLIN 1 YL)BUTYL]METHANESULFONAMIDE; PREDNISONE; S 32865; TOLL LIKE RECEPTOR AGONIST; UNCLASSIFIED DRUG;

ACUTE GRANULOCYTIC LEUKEMIA; ACUTE LYMPHOBLASTIC LEUKEMIA; ADOLESCENT; ADULT; AGED; ARTICLE; CANCER CHEMOTHERAPY; CANCER GROWTH; CHILD; CHILL; CLINICAL ARTICLE; CLINICAL ASSESSMENT; COUGHING; CYTOKINE PRODUCTION; DRUG ACTIVITY; DRUG DOSE ESCALATION; DRUG SAFETY; DRUG TOLERABILITY; DYSPNEA; EDEMA; FEMALE; FEVER; HEMATOLOGIC MALIGNANCY; HODGKIN DISEASE; HUMAN; INNATE IMMUNITY; MALAISE; MALE; MULTIPLE MYELOMA; MYALGIA; NAUSEA; NONHODGKIN LYMPHOMA; PAIN; PHASE 2 CLINICAL TRIAL; PRIORITY JOURNAL; RECURRENT CANCER; SCHOOL CHILD; SIDE EFFECT; SWEAT; TREATMENT DURATION; TREATMENT RESPONSE; VOMITING;

ADJUVANTS, IMMUNOLOGIC; ADOLESCENT; ADULT; AGED; AMINOQUINOLINES; CHILD; FEMALE; HEMATOLOGIC NEOPLASMS; HUMANS; IMMUNITY, INNATE; INJECTIONS, SUBCUTANEOUS; KILLER CELLS, NATURAL; MALE; MIDDLE AGED; REMISSION INDUCTION; SALVAGE THERAPY; SULFONAMIDES; T-LYMPHOCYTES; TOLL-LIKE RECEPTOR 7; YOUNG ADULT;

EID: 84866754613     PISSN: 03618609     EISSN: 10968652     Source Type: Journal    
DOI: 10.1002/ajh.23280     Document Type: Article

References (23)

1. Cook DN, Pisetsky DS, Schwartz DA. Toll-like receptors in the pathogenesis of human disease. Nat Immunol 2004; 5: 975-979.
2. Beutler B. Inferences, questions and possibilities in Toll-like receptor signalling. Nature 2004; 430: 257-263.
3. Kokkinopoulos I, Jordan WJ, Ritter MA. Toll-like receptor mRNA expression patterns in human dendritic cells and monocytes. Mol Immunol 2005; 42: 957-968.
4. Krieg AM. CpG motifs in bacterial DNA and their immune effects. Annu Rev Immunol 2002; 20: 709-760.
5. Blazar BR, Krieg AM, Taylor PA. Synthetic unmethylated cytosine-phosphate-guanosine oligodeoxynucleotides are potent stimulators of antileukemia responses in naive and bone marrow transplant recipients. Blood 2001; 98: 1217-1225.
6. Weigel BJ, Rodeberg DA, Krieg AM, et al. CpG oligodeoxynucleotides potentiate the antitumor effects of chemotherapy or tumor resection in an orthotopic murine model of rhabdomyosarcoma. Clin Cancer Res 2003; 9: 3105-3114.
7. Inglefield JR, Dumitru CD, Alkan SS, et al. TLR7 agonist 852A inhibition of tumor cell proliferation is dependent on plasmacytoid dendritic cells and type I IFN. J Interferon Cytokine Res 2008; 28: 253-263.
8. Birmachu W, Gleason RM, Bulbulian BJ, et al. Transcriptional networks in plasmacytoid dendritic cells stimulated with synthetic TLR 7 agonists. BMC Immunol 2007; 8: 26.
9. Meyer T, Nindl I, Schmook T, et al. Induction of apoptosis by Toll-like receptor-7 agonist in tissue cultures. Br J Dermatol 2003; 149 Suppl 66: 9-14.
10. Liang X, Moseman EA, Farrar MA, et al. Toll-like receptor 9 signaling by CpG-B oligodeoxynucleotides induces an apoptotic pathway in human chronic lymphocytic leukemia B cells. Blood 2010; 115: 5041-5052.
11. Dudek AZ, Yunis C, Harrison LI, et al. First in human phase I trial of 852A, a novel systemic toll-like receptor 7 agonist, to activate innate immune responses in patients with advanced cancer. Clin Cancer Res 2007; 13: 7119-7125.
12. Spaner DE SY, White D, Shaha S, He L, Masellis A, Wong K, Gorczynski R. A phase I/II trial of TLR-7 agonist immunotherapy in chronic lymphocytic leukemia. Leukemia 2010; 24: 222-226.
13. Harrison LI, Astry C, Kumar S, et al. Pharmacokinetics of 852A, an imidazoquinoline Toll-like receptor 7-specific agonist, following intravenous, subcutaneous, and oral administrations in humans. J Clin Pharmacol 2007; 47: 962-969.
14. Scheel B, Aulwurm S, Probst J, et al. Therapeutic anti-tumor immunity triggered by injections of immunostimulating single-stranded RNA. Eur J Immunol 2006; 36: 2807-2816.
15. Sauder DN, Smith MH, Senta-McMillian T, et al. Randomized, single-blind, placebo-controlled study of topical application of the immune response modulator resiquimod in healthy adults. Antimicrob Agents Chemother 2003; 47: 3846-3852.
16. Dummer R, Hauschild A, Becker JC, et al. An exploratory study of systemic administration of the toll-like receptor-7 agonist 852A in patients with refractory metastatic melanoma. Clin Cancer Res 2008; 14: 856-864.
17. Savage P, Horton V, Moore J, et al. A phase I clinical trial of imiquimod, an oral interferon inducer, administered daily. Br J Cancer 1996; 74: 1482-1486.
18. Goldstein D, Hertzog P, Tomkinson E, et al. Administration of imiquimod, an interferon inducer, in asymptomatic human immunodeficiency virus-infected persons to determine safety and biologic response modification. J Infect Dis 1998; 178: 858-861.
19. Smits EL, Ponsaerts P, Berneman ZN, et al. The use of TLR7 and TLR8 ligands for the enhancement of cancer immunotherapy. Oncologist 2008; 13: 859-875.
20. Spaner DE, Masellis A. Toll-like receptor agonists in the treatment of chronic lymphocytic leukemia. Leukemia 2007; 21: 53-60.
21. Miller JS, McCullar V. Human natural killer cells with polyclonal lectin and immunoglobulinlike receptors develop from single hematopoietic stem cells with preferential expression of NKG2A and KIR2DL2/L3/S2. Blood 2001; 98: 705-713.
22. Webb RN, Cruse JM, Lewis RE. Differential cytokine and Toll-like receptor expression in leukemia. Exp Mol Pathol 2007; 83: 464-470.
23. Sioud M, Floisand Y, Forfang L, et al. Signaling through toll-like receptor 7/8 induces the differentiation of human bone marrow CD34+ progenitor cells along the myeloid lineage. J Mol Biol 2006; 364: 945-954.