Phase 1 evaluation of intralesionally injected TLR9-agonist PF-3512676 in patients with basal cell carcinoma or metastatic melanoma

Journal of Immunotherapy

Volumn 31, Issue 5, 2008, Pages 520-527

  Hofmann, Maja A ^a   Kors, Christian ^a   Audring, Heike ^a   Walden, Peter ^a   Sterry, Wolfram ^a   Trefzer, Uwe ^a  

^a CHARITÉ UNIVERSITÄTSMEDIZIN BERLIN   (Germany)

Author keywords

Basal cell carcinoma; Metastatic melanoma; PF 3512676; Toll like receptor agonists

Indexed keywords

AGATOLIMOD; C REACTIVE PROTEIN; GAMMA INTERFERON; IMMUNOGLOBULIN; INTERLEUKIN 12P40; INTERLEUKIN 6; TUMOR NECROSIS FACTOR ALPHA; CPG 7909; CYTOKINE; OLIGODEOXYRIBONUCLEOTIDE; TOLL LIKE RECEPTOR 9;

ADULT; AGED; ANTINEOPLASTIC ACTIVITY; ARTICLE; BASAL CELL CARCINOMA; CLINICAL TRIAL; CONTROLLED STUDY; DRUG DOSE ESCALATION; DRUG DOSE INCREASE; DRUG ERUPTION; DRUG FEVER; DRUG SAFETY; DRUG STRUCTURE; DRUG TOLERABILITY; FATIGUE; FEMALE; FLOW CYTOMETRY; FLU LIKE SYNDROME; HEADACHE; HOT FLUSH; HUMAN; HUMAN TISSUE; IMMUNE RESPONSE; IMMUNOHISTOCHEMISTRY; INJECTION SITE EDEMA; INJECTION SITE ERYTHEMA; INJECTION SITE SWELLING; LACTATE DEHYDROGENASE BLOOD LEVEL; LYMPHOCYTOPENIA; MALAISE; MALE; MELANOMA; METASTASIS; NAUSEA; PAIN; PARESTHESIA; PERIORBITAL EDEMA; PHASE 1 CLINICAL TRIAL; PRIORITY JOURNAL; PROTEIN BLOOD LEVEL; RIGOR; SIDE EFFECT; SWEATING; TREATMENT RESPONSE; TUMOR LOCALIZATION; TUMOR REGRESSION; ADOLESCENT; CHEMICAL STRUCTURE; CHEMISTRY; DRUG POTENTIATION; IMMUNOLOGY; LYMPHOCYTE; METABOLISM; MIDDLE AGED; PATHOLOGY;

ADOLESCENT; ADULT; AGED; C-REACTIVE PROTEIN; CARCINOMA, BASAL CELL; CYTOKINES; FEMALE; HUMANS; IMMUNOGLOBULINS; LYMPHOCYTES; MALE; MELANOMA; MIDDLE AGED; MOLECULAR STRUCTURE; NEOPLASM METASTASIS; OLIGODEOXYRIBONUCLEOTIDES; TOLL-LIKE RECEPTOR 9;

EID: 55249083982     PISSN: 15249557     EISSN: None     Source Type: Journal    
DOI: 10.1097/CJI.0b013e318174a4df     Document Type: Article

References (34)

1. Nauts HC, Fowler GA, Bogatko FH. A review of the influence of bacterial infection and of bacterial products (Coley's toxins) on malignant tumors in man; a critical analysis of 30 inoperable cases treated by Coley's mixed toxins, in which diagnosis was confirmed by microscopic examination selected for special study. Acta Med Scand Suppl. 1953;276:1-103.
2. Tokunaga T, Yamamoto T, Yamamoto S. How BCG led to the discovery of immunostimulatory DNA. Jpn J Infect Dis. 1999;52: 1-11.
3. Krieg AM. CpG motifs: the active ingredient in bacterial extracts? Nat Med. 2003;9:831-835.
4. Krieg AM, Yi AK, Matson S, et al. CpG motifs in bacterial DNA trigger direct B-cell activation. Nature. 1995;374:546-549.
5. Hemmi H, Takeuchi O, Kawai T, et al. A Toll-like receptor recognizes bacterial DNA. Nature. 2000;408:740-745.
6. 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 USA. 2001;98:9237-9242.
7. Takeshita F, Leifer CA, Gursel I, et al. Cutting edge: role of Tolllike receptor 9 in CpG DNA-induced activation of human cells. J Immunol. 2001;167:3555-3558.
8. Leonard JP, Link B, Emmanouilides C, et al. Phase I trial of Tolllike receptor 9 agonist PF-3512676 (CpG 7909) with and following rituximab in patients with recurrent indolent and aggressive non-Hodgkin's lymphoma. Clin Cancer Res. 2007;13:6168-6174.
9. Ballas ZK, Krieg AM, Warren T, et al. Divergent therapeutic and immunologic effects of oligodeoxynucleotides with distinct CpG motifs. J Immunol. 2001;167:4878-4886.
10. Kawarada Y, Ganss R, Garbi N, et al. NK - and CD8(+) T cell-mediated eradication of established tumors by peritumoral injection of CpG-containing oligodeoxynucleotides. J Immunol. 2001;167: 5247-5253.
11. Baines J, Celis E. Immune-mediated tumor regression induced by CpG-containing oligodeoxynucleotides. Clin Cancer Res. 2003;9: 2693-2700.
12. Auf G, Carpentier AF, Chen L, et al. Implication of macrophages in tumor rejection induced by CpG-oligodeoxynucleotides without antigen. Clin Cancer Res. 2001;7:3540-3543.
13. Sharma S, Karakousis CP, Takita H, et al. Intra-tumoral injection of CpG results in the inhibition of tumor growth in murine colon-26 and B-16 tumors. Biotechnol Lett. 2003;25:149-153.
14. Krieg AM. Therapeutic potential of Toll-like receptor 9 activation. Nat Rev Drug Discov. 2006;5:471-484.
15. Manegold C, Gravenor D, Woytowitz D, et al. Randomized phase II trial of a Toll-like receptor 9 (TLR9) agonist oligodeoxynucleo-tide, PF-3512676 (CPG 7909), in combination with first-line taxane/ platinum chemotherapy for advanced-stage non-small-cell lung cancer. J Clin Oncol. 2007. Accepted for publication.
16. Thompson JA, Kuzel T, Bukowski R, et al. Phase Ib trial of a targeted TLR9 CpG immunomodulator (CPG 7909) in advanced renal cell carcinoma (RCC) [abstract]. J Clin Oncol. 2004;22(suppl): 416. Abstract 4644.
17. Kim Y, Girardi M, McAuley S, et al. Cutaneous T-cell lymphoma (CTCL) responses to a TLR9 agonist CpG immunomodulator (CPG 7909), a phase I study [abstract]. J Clin Oncol. 2004;22(suppl): 580. Abstract 6600.
18. Link BK, Ballas ZK, Weisdorf D, et al. Oligodeoxynucleotide CpG 7909 delivered as intravenous infusion demonstrates immunologic modulation in patients with previously treated non-Hodgkin lymphoma. J Immunother (1997). 2006;29:558-568.
19. Pashenkov M, Goess G, Wagner C, et al. Phase II trial of a Toll-like receptor 9-activating oligonucleotide in patients with metastatic melanoma. J Clin Oncol. 2006;24:5716-5724.
20. Saldanha G, Fletcher A, Slater DN. Basal cell carcinoma: a dermatopathological and molecular biological update. Br J Dermatol. 2003;148:195-202.
21. Kuijpers DI, Thissen MR, Neumann MH. Basal cell carcinoma: treatment options and prognosis, a scientific approach to a common malignancy. Am J Clin Dermatol. 2002;3:247-259.
22. Sterry W, Ruzicka T, Herrera E, et al. Imiquimod 5% cream for the treatment of superficial and nodular basal cell carcinoma: randomized studies comparing low-frequency dosing with and without occlusion. Br J Dermatol. 2002;147:1227-1236.
23. Hemmi H, Kaisho T, Takeuchi O, et al. Small anti-viral compounds activate immune cells via the TLR7 MyD88-dependent signaling pathway. Nat Immunol. 2002;3:196-200.
24. Hornung V, Rothenfusser S, Britsch S, et al. Quantitative expression of Toll-like receptor 1-10 mRNA in cellular subsets of human peripheral blood mononuclear cells and sensitivity to CpG oligodeoxynucleotides. J Immunol. 2002;168:4531-4537.
25. Jurk M, Heil F, Vollmer J, et al. Human TLR7 or TLR8 independently confer responsiveness to the antiviral compound R-848. Nat Immunol. 2002;3:499.
26. Kadowaki N, Ho S, Antonenko S, et al. Subsets of human dendritic cell precursors express different Toll-like receptors and respond to different microbial antigens. J Exp Med. 2001;194: 863-869.
27. Bajetta E, Del Vecchio M, Bernard-Marty C, et al. Metastatic melanoma: chemotherapy. Semin Oncol. 2002;29:427-445.
28. Gursel M, Verthelyi D, Klinman DM. CpG oligodeoxynucleotides induce human monocytes to mature into functional dendritic cells. Eur J Immunol. 2002;32:2617-2622.
29. Iwasaki A, Medzhitov R. Toll-like receptor control of the adaptive immune responses. Nat Immunol. 2004;5:987-995.
30. Pichyangkul S, Yongvanitchit K, Kum-arb U, et al. Whole blood cultures to assess the immunostimulatory activities of CpG oligodeoxynucleotides. J Immunol Methods. 2001;247:83-94.
31. Krieg AM. Development of TLR9 agonists for cancer therapy. J Clin Invest. 2007;117:1184-1194.
32. Grimm EA, Smid CM, Lee JJ, et al. Unexpected cytokines in serum of malignant melanoma patients during sequential biochemother-apy. Clin Cancer Res. 2000;6:3895-3903.
33. Milas L, Mason KA, Ariga H, et al. CpG oligodeoxynucleotide enhances tumor response to radiation. Cancer Res. 2004;64: 5074-5077.
34. Buhtoiarov IN, Sondel PM, Eickhoff JC, et al. Macrophages are essential for antitumour effects against weakly immunogenic murine tumours induced by class B CpG-oligodeoxynucleotides. Immunology. 2007;120:412-423.