Novel toll-like receptor 2 ligands for targeted pancreatic cancer imaging and immunotherapy

Journal of Medicinal Chemistry

Volumn 55, Issue 22, 2012, Pages 9751-9762

  Huynh, Amanda Shanks ^a   Chung, Woo Jin ^b   Cho, Hyun Il ^a   Moberg, Valerie E ^a   Celis, Esteban ^a   Morse, David L ^a   Vagner, Josef ^b  

^a H LEE MOFFITT CANCER CENTER AND RESEARCH INSTITUTE   (United States)

^b UNIVERSITY OF ARIZONA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ADJUVANT; DYE; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; SYNTHETIC PEPTIDE; TOLL LIKE RECEPTOR AGONIST;

ANIMAL MODEL; ARTICLE; BINDING AFFINITY; CANCER IMMUNOTHERAPY; CD8+ T LYMPHOCYTE; DRUG ACTIVITY; DRUG RECEPTOR BINDING; DRUG SELECTIVITY; FLUORESCENCE IMAGING; HUMAN; HUMAN CELL; IMMUNE RESPONSE; IMMUNOSTIMULATION; MOUSE; NONHUMAN; PANCREAS CANCER; SIGNAL TRANSDUCTION;

ANIMALS; CD4-POSITIVE T-LYMPHOCYTES; CELLS, CULTURED; DIAGNOSTIC IMAGING; FEMALE; FLUORESCENT DYES; HUMANS; IMMUNOTHERAPY; KIDNEY; LIGANDS; MICE; MICE, INBRED C57BL; MOLECULAR STRUCTURE; NF-KAPPA B; PANCREATIC NEOPLASMS; SIGNAL TRANSDUCTION; STRUCTURE-ACTIVITY RELATIONSHIP; TOLL-LIKE RECEPTOR 2;

EID: 84869989377     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm301002f     Document Type: Article

References (69)

1. Cheng, N.; He, R.; Tian, J.; Ye, P. P.; Ye, R. D. Cutting edge: TLR2 is a functional receptor for acute-phase serum amyloid A J. Immunol. 2008, 181 (1) 22-26
2. Kanzler, H.; Barrat, F. J.; Hessel, E. M.; Coffman, R. L. Therapeutic targeting of innate immunity with Toll-like receptor agonists and antagonists Nat. Med. 2007, 13 (5) 552-559
3. Zuany-Amorim, C.; Hastewell, J.; Walker, C. Toll-like receptors as potential therapeutic targets for multiple diseases Nat. Rev. Drug Discovery 2002, 1 (10) 797-807
4. Jarnicki, A. G.; Conroy, H.; Brereton, C.; Donnelly, G.; Toomey, D.; Walsh, K.; Sweeney, C.; Leavy, O.; Fletcher, J.; Lavelle, E. C.; Dunne, P.; Mills, K. H. Attenuating regulatory T cell induction by TLR agonists through inhibition of p38 MAPK signaling in dendritic cells enhances their efficacy as vaccine adjuvants and cancer immunotherapeutics J. Immunol. 2008, 180 (6) 3797-3806
5. Marshall, N. A.; Galvin, K. C.; Corcoran, A. M.; Boon, L.; Higgs, R.; Mills, K. H. Immunotherapy with PI3K inhibitor and Toll-like receptor agonist induces IFN-gamma+IL-17+polyfunctional T cells that mediate rejection of murine tumors Cancer Res. 2012, 72 (3) 581-591
6. Adams, S. Toll-like receptor agonists in cancer therapy Immunotherapy 2009, 1 (6) 949-964
7. Akira, S.; Takeda, K. Toll-like receptor signalling Nat. Rev. Immunol. 2004, 4 (7) 499-511
8. West, A. P.; Koblansky, A. A.; Ghosh, S. Recognition and signaling by Toll-like receptors Annu. Rev. Cell Dev. Biol. 2006, 22, 409-437
9. Jin, M. S.; Lee, J. O. Structures of the Toll-like receptor family and its ligand complexes Immunity 2008, 29 (2) 182-191
10. Ozinsky, A.; Underhill, D. M.; Fontenot, J. D.; Hajjar, A. M.; Smith, K. D.; Wilson, C. B.; Schroeder, L.; Aderem, A. The repertoire for pattern recognition of pathogens by the innate immune system is defined by cooperation between Toll-like receptors Proc. Natl. Acad. Sci. U.S.A. 2000, 97 (25) 13766-13771
11. Janeway, C. A., Jr.; Medzhitov, R. Innate immune recognition Annu. Rev. Immunol. 2002, 20, 197-216
12. Akira, S.; Takeda, K.; Kaisho, T. Toll-like receptors: critical proteins linking innate and acquired immunity Nat. Immunol. 2001, 2 (8) 675-680
13. Kawai, T.; Akira, S. The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors Nat. Immunol. 2010, 11 (5) 373-384
14. Cho, H. I.; Lee, Y. R.; Celis, E. Interferon gamma limits the effectiveness of melanoma peptide vaccines Blood 2011, 117 (1) 135-144
15. Serbina, N.; Pamer, E. G. Quantitative studies of CD8+ T-cell responses during microbial infection Curr. Opin. Immunol. 2003, 15 (4) 436-442
16. Ingale, S.; Wolfert, M. A.; Buskas, T.; Boons, G. J. Increasing the antigenicity of synthetic tumor-associated carbohydrate antigens by targeting Toll-like receptors ChemBioChem 2009, 10 (3) 455-463
17. Buskas, T.; Thompson, P.; Boons, G. J. Immunotherapy for cancer: synthetic carbohydrate-based vaccines Chem. Commun. 2009, 36, 5335-5349
18. Hennessy, E. J.; Parker, A. E.; O'Neill, L. A. Targeting Toll-like receptors: emerging therapeutics? Nat. Rev. Drug Discovery 2010, 9 (4) 293-307
19. Simons, M. P.; O'Donnell, M. A.; Griffith, T. S. Role of neutrophils in BCG immunotherapy for bladder cancer Urol. Oncol. 2008, 26 (4) 341-345
20. Murata, M. Activation of Toll-like receptor 2 by a novel preparation of cell wall skeleton from Mycobacterium bovis BCG Tokyo (SMP-105) sufficiently enhances immune responses against tumors Cancer Sci. 2008, 99 (7) 1435-1440
21. Schmidt, J.; Welsch, T.; Jager, D.; Muhlradt, P. F.; Buchler, M. W.; Marten, A. Intratumoural injection of the Toll-like receptor-2/6 agonist "macrophage-activating lipopeptide-2" in patients with pancreatic carcinoma: a phase I/II trial Br. J. Cancer 2007, 97 (5) 598-604
22. Celis, E. Toll-like receptor ligands energize peptide vaccines through multiple paths Cancer Res. 2007, 67 (17) 7945-7947
23. Cho, H. I.; Celis, E. Optimized peptide vaccines eliciting extensive CD8 T-cell responses with therapeutic antitumor effects Cancer Res. 2009, 69 (23) 9012-9009
24. Cancer Facts & Figures - 2012; American Cancer Society: Atlanta, GA, 2012; pp 1-63.
25. Ferrone, C. R.; Brennan, M. F.; Gonen, M.; Coit, D. G.; Fong, Y.; Chung, S.; Tang, L.; Klimstra, D.; Allen, P. J. Pancreatic adenocarcinoma: the actual 5-year survivors J. Gastrointest. Surg. 2008, 12 (4) 701-706
26. Howard, T. J.; Krug, J. E.; Yu, J.; Zyromski, N. J.; Schmidt, C. M.; Jacobson, L. E.; Madura, J. A.; Wiebke, E. A.; Lillemoe, K. D. A margin-negative R0 resection accomplished with minimal postoperative complications is the surgeon's contribution to long-term survival in pancreatic cancer J. Gastrointest. Surg. 2006, 10 (10) 1338-1345
27. Angst, E.; Kim-Fuchs, C.; Chittazhathu Kurian Kuruvilla, Y.; Inderbitzin, D.; Montani, M.; Candinas, D.; Gloor, B. How to counter the problem of r1 resection in duodenopancreatectomy for pancreatic cancer? J. Gastrointest. Surg. 2012, 16 (3) 673
28. Esposito, I.; Kleeff, J.; Bergmann, F.; Reiser, C.; Herpel, E.; Friess, H.; Schirmacher, P.; Buchler, M. W. Most pancreatic cancer resections are R1 resections Ann. Surg. Oncol. 2008, 15 (6) 1651-1660
29. Campbell, F.; Smith, R. A.; Whelan, P.; Sutton, R.; Raraty, M.; Neoptolemos, J. P.; Ghaneh, P. Classification of R1 resections for pancreatic cancer: the prognostic relevance of tumour involvement within 1 mm of a resection margin Histopathology 2009, 55 (3) 277-283
30. van Dam, G. M.; Themelis, G.; Crane, L. M.; Harlaar, N. J.; Pleijhuis, R. G.; Kelder, W.; Sarantopoulos, A.; de Jong, J. S.; Arts, H. J.; van der Zee, A. G.; Bart, J.; Low, P. S.; Ntziachristos, V. Intraoperative tumor-specific fluorescence imaging in ovarian cancer by folate receptor-alpha targeting: first in-human results Nat. Med. 2011, 17 (10) 1315-1319
31. Sevick-Muraca, E. M.; Sharma, R.; Rasmussen, J. C.; Marshall, M. V.; Wendt, J. A.; Pham, H. Q.; Bonefas, E.; Houston, J. P.; Sampath, L.; Adams, K. E.; Blanchard, D. K.; Fisher, R. E.; Chiang, S. B.; Elledge, R.; Mawad, M. E. Imaging of lymph flow in breast cancer patients after microdose administration of a near-infrared fluorophore: feasibility study Radiology 2008, 246 (3) 734-741
32. Tagaya, N.; Yamazaki, R.; Nakagawa, A.; Abe, A.; Hamada, K.; Kubota, K.; Oyama, T. Intraoperative identification of sentinel lymph nodes by near-infrared fluorescence imaging in patients with breast cancer Am. J. Surg. 2008, 195 (6) 850-853
33. Stummer, W.; Pichlmeier, U.; Meinel, T.; Wiestler, O. D.; Zanella, F.; Reulen, H. J. Fluorescence-guided surgery with 5-aminolevulinic acid for resection of malignant glioma: a randomised controlled multicentre phase III trial Lancet Oncol. 2006, 7 (5) 392-401
34. Hadjipanayis, C. G.; Jiang, H.; Roberts, D. W.; Yang, L. Current and future clinical applications for optical imaging of cancer: from intraoperative surgical guidance to cancer screening Semin. Oncol. 2011, 38 (1) 109-118
35. Keereweer, S.; Hutteman, M.; Kerrebijn, J. D.; van de Velde, C. J.; Vahrmeijer, A. L.; Lowik, C. W. Translational optical imaging in diagnosis and treatment of cancer Curr. Pharm. Biotechnol. 2012, 13 (4) 498-503
36. Ntziachristos, V.; Yoo, J. S.; van Dam, G. M. Current concepts and future perspectives on surgical optical imaging in cancer J. Biomed. Opt. 2010, 15 (6) 066024
37. Nguyen, Q. T.; Olson, E. S.; Aguilera, T. A.; Jiang, T.; Scadeng, M.; Ellies, L. G.; Tsien, R. Y. Surgery with molecular fluorescence imaging using activatable cell-penetrating peptides decreases residual cancer and improves survival Proc. Natl. Acad. Sci. U.S.A. 2010, 107 (9) 4317-4322
38. Morse, D. L.; Balagurunathan, Y.; Hostetter, G.; Trissal, M.; Tafreshi, N. K.; Burke, N.; Lloyd, M.; Enkemann, S.; Coppola, D.; Hruby, V. J.; Gillies, R. J.; Han, H. Identification of novel pancreatic adenocarcinoma cell-surface targets by gene expression profiling and tissue microarray Biochem. Pharmacol. 2012, 80 (5) 748-754
39. Muhlradt, P. F.; Kiess, M.; Meyer, H.; Sussmuth, R.; Jung, G. Isolation, structure elucidation, and synthesis of a macrophage stimulatory lipopeptide from Mycoplasma fermentans acting at picomolar concentration J. Exp. Med. 1997, 185 (11) 1951-1958
40. Muhlradt, P. F.; Kiess, M.; Meyer, H.; Sussmuth, R.; Jung, G. Structure and specific activity of macrophage-stimulating lipopeptides from Mycoplasma hyorhinis Infect. Immun. 1998, 66 (10) 4804-4810
41. Takeuchi, O.; Kawai, T.; Muhlradt, P. F.; Morr, M.; Radolf, J. D.; Zychlinsky, A.; Takeda, K.; Akira, S. Discrimination of bacterial lipoproteins by Toll-like receptor 6 Int. Immunol. 2001, 13 (7) 933-940
42. Alexopoulou, L.; Thomas, V.; Schnare, M.; Lobet, Y.; Anguita, J.; Schoen, R. T.; Medzhitov, R.; Fikrig, E.; Flavell, R. A. Hyporesponsiveness to vaccination with Borrelia burgdorferi OspA in humans and in TLR1- and TLR2-deficient mice Nat. Med. 2002, 8 (8) 878-884
43. Morr, M.; Takeuchi, O.; Akira, S.; Simon, M. M.; Muhlradt, P. F. Differential recognition of structural details of bacterial lipopeptides by Toll-like receptors Eur. J. Immunol. 2002, 32 (12) 3337-3347
44. Takeuchi, O.; Sato, S.; Horiuchi, T.; Hoshino, K.; Takeda, K.; Dong, Z.; Modlin, R. L.; Akira, S. Cutting edge: role of Toll-like receptor 1 in mediating immune response to microbial lipoproteins J. Immunol. 2002, 169 (1) 10-14
45. Jin, M. S.; Kim, S. E.; Heo, J. Y.; Lee, M. E.; Kim, H. M.; Paik, S. G.; Lee, H.; Lee, J. O. Crystal structure of the TLR1-TLR2 heterodimer induced by binding of a tri-acylated lipopeptide Cell 2007, 130 (6) 1071-1082
46. Manavalan, B.; Basith, S.; Choi, S. Similar structures but different roles - an updated perspective on TLR structures Front. Physiol. 2011, 2, 41
47. Kang, J. Y.; Nan, X.; Jin, M. S.; Youn, S. J.; Ryu, Y. H.; Mah, S.; Han, S. H.; Lee, H.; Paik, S. G.; Lee, J. O. Recognition of lipopeptide patterns by Toll-like receptor 2-Toll-like receptor 6 heterodimer Immunity 2009, 31 (6) 873-884
48. Buwitt-Beckmann, U.; Heine, H.; Wiesmuller, K. H.; Jung, G.; Brock, R.; Ulmer, A. J. Lipopeptide structure determines TLR2 dependent cell activation level FEBS J. 2005, 272 (24) 6354-6364
49. Yamamoto, M.; Takeda, K. Current views of Toll-like receptor signaling pathways Gastroenterol. Res. Pract. 2010, 240365
50. Uhlar, C. M.; Whitehead, A. S. Serum amyloid A, the major vertebrate acute-phase reactant Eur. J. Biochem. 1999, 265 (2) 501-523
51. Manukyan, M.; Triantafilou, K.; Triantafilou, M.; Mackie, A.; Nilsen, N.; Espevik, T.; Wiesmuller, K. H.; Ulmer, A. J.; Heine, H. Binding of lipopeptide to CD14 induces physical proximity of CD14, TLR2 and TLR1 Eur. J. Immunol. 2005, 35 (3) 911-921
52. Fujimoto, Y.; Hashimoto, M.; Furuyashiki, M.; Katsumoto, M.; Seya, T.; Suda, Y.; Fukase, K. Lipopeptides from Staphylococcus aureus as Tlr2 ligands: prediction with mRNA expression, chemical synthesis, and immunostimulatory activities ChemBioChem 2009, 10 (14) 2311-2315
53. Czarniecki, M. Small molecule modulators of Toll-like receptors J. Med. Chem. 2008, 51 (21) 6621-6626
54. Handl, H. L.; Vagner, J.; Yamamura, H. I.; Hruby, V. J.; Gillies, R. J. Development of a lanthanide-based assay for detection of receptor-ligand interactions at the delta-opioid receptor Anal. Biochem. 2005, 343 (2) 299-307
55. Xu, L.; Vagner, J.; Josan, J.; Lynch, R. M.; Morse, D. L.; Baggett, B.; Han, H.; Mash, E. A.; Hruby, V. J.; Gillies, R. J. Enhanced targeting with heterobivalent ligands Mol. Cancer Ther. 2009, 8 (8) 2356-2365
56. Barkey, N. M.; Tafreshi, N. K.; Josan, J. S.; De Silva, C. R.; Sill, K. N.; Hruby, V. J.; Gillies, R. J.; Morse, D. L.; Vagner, J. Development of melanoma-targeted polymer micelles by conjugation of a melanocortin 1 receptor (MC1R) specific ligand J. Med. Chem. 2011, 54 (23) 8078-8084
57. Josan, J. S.; Morse, D. L.; Xu, L.; Trissal, M.; Baggett, B.; Davis, P.; Vagner, J.; Gillies, R. J.; Hruby, V. J. Solid-phase synthetic strategy and bioevaluation of a labeled delta-opioid receptor ligand Dmt-Tic-Lys for in vivo imaging Org. Lett. 2009, 11 (12) 2479-2482
58. Agnihotri, G.; Crall, B. M.; Lewis, T. C.; Day, T. P.; Balakrishna, R.; Warshakoon, H. J.; Malladi, S. S.; David, S. A. Structure-activity relationships in Toll-like receptor 2-agonists leading to simplified monoacyl lipopeptides J. Med. Chem. 2011, 54 (23) 8148-8160
59. Salunke, D. B.; Shukla, N. M.; Yoo, E.; Crall, B. M.; Balakrishna, R.; Malladi, S. S.; David, S. A. Structure-activity relationships in human Toll-like receptor 2-specific monoacyl lipopeptides J. Med. Chem. 2012, 55 (7) 3353-3363
60. Kimbrell, M. R.; Warshakoon, H.; Cromer, J. R.; Malladi, S.; Hood, J. D.; Balakrishna, R.; Scholdberg, T. A.; David, S. A. Comparison of the immunostimulatory and proinflammatory activities of candidate Gram-positive endotoxins, lipoteichoic acid, peptidoglycan, and lipopeptides, in murine and human cells Immunol. Lett. 2008, 118 (2) 132-141
61. Vagner, J.; Xu, L.; Handl, H. L.; Josan, J. S.; Morse, D. L.; Mash, E. A.; Gillies, R. J.; Hruby, V. J. Heterobivalent ligands crosslink multiple cell-surface receptors: the human melanocortin-4 and delta-opioid receptors Angew. Chem., Int. Ed. 2008, 47 (9) 1685-1688
62. Krchnak, V.; Vagner, J.; Lebl, M. Noninvasive continuous monitoring of solid-phase peptide synthesis by acid-base indicator Int. J. Pept. Protein Res. 1988, 32 (5) 415-416
63. Krchnak, V.; Vagner, J. Color-monitored solid-phase multiple peptide synthesis under low-pressure continuous-flow conditions Pept. Res. 1990, 3 (4) 182-193
64. Metzger, J. W.; Wiesmuller, K. H.; Jung, G. Synthesis of N alpha-Fmoc protected derivatives of S -(2,3-dihydroxypropyl)-cysteine and their application in peptide synthesis Int. J. Pept. Protein Res. 1991, 38 (6) 545-554
65. Reichel, F.; Roelofsen, A. M.; Geurts, H. P. M.; Hämälä inen, T. I.; Feiters, M. C.; Boons, G.-J. Stereochemical dependence of the self-assembly of the immunoadjuvants Pam3Cys and Pam3Cys-Ser J. Am. Chem. Soc. 1999, 121 (35) 7989-7997
66. Guevara-Patino, J. A.; Engelhorn, M. E.; Turk, M. J.; Liu, C.; Duan, F.; Rizzuto, G.; Cohen, A. D.; Merghoub, T.; Wolchok, J. D.; Houghton, A. N. Optimization of a self antigen for presentation of multiple epitopes in cancer immunity J. Clin. Invest. 2006, 116 (5) 1382-1390
67. Schindler, U.; Baichwal, V. R. Three NF-kappa B binding sites in the human E-selectin gene required for maximal tumor necrosis factor alpha-induced expression Mol. Cell. Biol. 1994, 14 (9) 5820-5831
68. Handl, H. L.; Vagner, J.; Yamamura, H. I.; Hruby, V. J.; Gillies, R. J. Lanthanide-based time-resolved fluorescence of in cyto ligand-receptor interactions Anal. Biochem. 2004, 330 (2) 242-250
69. Appay, V.; Rowland-Jones, S. L. The assessment of antigen-specific CD8+ T cells through the combination of MHC class I tetramer and intracellular staining J. Immunol. Methods 2002, 268 (1) 9-19