Prothymosin α and a prothymosin α-derived peptide enhance TH1-type immune responses against defined HER-2/neu epitopes

BMC Immunology

Volumn 14, Issue 1, 2013, Pages

  Ioannou, Kyriaki ^a   Derhovanessian, Evelyna ^b   Tsakiri, Eleni ^a   Samara, Pinelopi ^a   Kalbacher, Hubert ^b   Voelter, Wolfgang ^b   Trougakos, Ioannis P ^a   Pawelec, Graham ^b   Tsitsilonis, Ourania E ^a  

^a UNIVERSITY OF ATHENS   (Greece)

^b UNIVERSITY OF TÜBINGEN   (Germany)

Author keywords

Adjuvant; Dendritic cells; HER 2 neu peptides; Immunoreactive peptide; Prothymosin alpha; TH1 immune responses; TLR 4

Indexed keywords

EPIDERMAL GROWTH FACTOR RECEPTOR 2; EPITOPE; MYELOID DIFFERENTIATION FACTOR 88; PROTEIN PRECURSOR; PROTHYMOSIN ALPHA; PROTHYMOSIN ALPHA DERIVED PEPTIDE; TIRAPAZAMINE; TOLL LIKE RECEPTOR 4; UNCLASSIFIED DRUG;

ARTICLE; CD4+ T LYMPHOCYTE; CD8+ T LYMPHOCYTE; CELL MATURATION; CELLULAR IMMUNITY; CONTROLLED STUDY; CYTOKINE PRODUCTION; CYTOKINE RELEASE; DENDRITIC CELL; HUMAN; HUMAN CELL; LYMPHOCYTE PROLIFERATION; PHENOTYPE; PROTEIN PROTEIN INTERACTION; TH1 CELL;

ADAPTOR PROTEINS, VESICULAR TRANSPORT; CD4-POSITIVE T-LYMPHOCYTES; CD8-POSITIVE T-LYMPHOCYTES; CELL DIFFERENTIATION; CELL PROLIFERATION; CELLS, CULTURED; CYTOKINES; DENDRITIC CELLS; EPITOPES; FLOW CYTOMETRY; HUMANS; IMMUNOBLOTTING; IMMUNOTHERAPY, ADOPTIVE; LYMPHOCYTE ACTIVATION; MEMBRANE GLYCOPROTEINS; MYELOID DIFFERENTIATION FACTOR 88; PEPTIDES; PROTEIN PRECURSORS; RECEPTOR, ERBB-2; RECEPTORS, INTERLEUKIN-1; T-LYMPHOCYTES, CYTOTOXIC; TH1 CELLS; THYMOSIN; TOLL-LIKE RECEPTOR 4;

EID: 84885835785     PISSN: None     EISSN: 14712172     Source Type: Journal    
DOI: 10.1186/1471-2172-14-43     Document Type: Article

References (67)

1. Chianese-Bullock KA, Irvin WP, Petroni GR, Murphy C, Smolkin M, Olson WC, Coleman E, Boerner SA, Nail CJ, Neese PY, Yuan A, Hogan KT, Slingluff CL. A multipeptide vaccine is safe and elicits T-cell responses in participants with advanced stage ovarian cancer. J Immunother 2008, 31:420-430. 10.1097/CJI.0b013e31816dad10, 18391753.
2. Barve M, Bender J, Senzer N, Cunningham C, Greco FA, McCune D, Steis R, Khong H, Richards D, Stephenson J, Ganesa P, Nemunaitis J, Ishioka G, Pappen B, Nemunaitis M, Morse M, Mills B, Maples PB, Sherman J, Nemunaitis JJ. Induction of immune responses and clinical efficacy in a phase II trial of IDM-2101, a 10-epitope cytotoxic T-lymphocyte vaccine, in metastatic non-small-cell lung cancer. J Clin Oncol 2008, 26:4418-4425. 10.1200/JCO.2008.16.6462, 18802154.
3. Walter S, Weinschenk T, Stenzl A, Zdrojowy R, Pluzanska A, Szczylik C, Staehler M, Brugger W, Dietrich PY, Mendrzyk R, Hilf N, Schoor O, Fritsche J, Mahr A, Maurer D, Vass V, Trautwein C, Lewandrowski P, Flohr C, Pohla H, Stanczak JJ, Bronte V, Mandruzzato S, Biedermann T, Pawelec G, Derhovanessian E, Yamagishi H, Miki T, Hongo F, Takaha N, Hirakawa K, Tanaka H, Stevanovic S, Frisch J, Mayer-Mokler A, Kirner A, Rammensee HG, Reinhardt C, Singh-Jasuja H. Multipeptide immune response to cancer vaccine IMA901 after single-dose cyclophosphamide associates with longer patient survival. Nat Med 2012, 18:1254-1261. 10.1038/nm.2883, 22842478.
4. Coffman RL, Sher A, Seder RA. Vaccine adjuvants: putting innate immunity to work. Immunity 2010, 33:492-503. 10.1016/j.immuni.2010.10.002, 3420356, 21029960.
5. Jähnisch H, Füssel S, Kiessling A, Wehner R, Zastrow S, Bachmann M, Rieber EP, Wirth MP, Schmitz M. Dendritic cell-based immunotherapy for prostate cancer. Clin Dev Immunol 2010, 2010:517493. 2975068, 21076523.
6. Palucka AK, Ueno H, Fay J, Banchereau J. Dendritic cells: a critical player in cancer therapy?. J Immunother 2008, 31:793-805. 10.1097/CJI.0b013e31818403bc, 2716088, 18833008.
7. Palucka K, Ueno H, Fay J, Banchereau J. Dendritic cells and immunity against cancer. J Intern Med 2011, 269:64-73. 10.1111/j.1365-2796.2010.02317.x, 3023888, 21158979.
8. Schreibelt G, Benitez-Ribas D, Schuurhuis D, Lambeck AJ, van Hout-Kuijer M, Schaft N, Punt CJ, Figdor CG, Adema GJ, de Vries IJ. Commonly used prophylactic vaccines as an alternative for synthetically produced TLR ligands to mature monocyte-derived dendritic cells. Blood 2010, 116:564-574. 10.1182/blood-2009-11-251884, 20424184.
9. Pinzon-Charry A, Maxwell T, López JA. Dendritic cell dysfunction in cancer: a mechanism for immunosuppression. Immunol Cell Biol 2005, 83:451-461. 10.1111/j.1440-1711.2005.01371.x, 16174093.
10. Schilling B, Harasymczuk M, Schuler P, Egan J, Ferrone S, Whiteside TL. IRX-2, a novel immunotherapeutic, enhances functions of human dendritic cells. PLoS One 2013, 8:e47234. 10.1371/journal.pone.0047234, 3567103, 23408925.
11. Napoletano C, Zizzari IG, Rughetti A, Rahimi H, Irimura T, Clausen H, Wandall HH, Belleudi F, Bellati F, Pierelli L, Frati L, Nuti M. Targeting of macrophage galactose-type C-type lectin (MGL) induces DC signaling and activation. Eur J Immunol 2012, 42:936-945. 10.1002/eji.201142086, 22531918.
12. Vacchelli E, Galluzzi L, Eggermont A, Fridman WH, Galon J, Sautès-Fridman C, Tartour E, Zitvogel L, Kroemer G. Trial watch: FDA-approved Toll-like receptor agonists for cancer therapy. Oncoimmunology 2012, 1:894-907. 10.4161/onci.20931, 3489745, 23162757.
13. Karbach J, Gnjatic S, Bender A, Neumann A, Weidmann E, Yuan J, Ferrara CA, Hoffmann E, Old LJ, Altorki NK, Jäger E. Tumor-reactive CD8+ T-cell responses after vaccination with NY-ESO-1 peptide, CpG 7909 and Montanide ISA-51: association with survival. Int J Cancer 2010, 126:909-918.
14. Wieckowski E, Chatta GS, Mailliard RM, Gooding W, Palucka K, Banchereau J, Kalinski P. Type-1 polarized dendritic cells loaded with apoptotic prostate cancer cells are potent inducers of CD8(+) T cells against prostate cancer cells and defined prostate cancer-specific epitopes. Prostate 2011, 71:125-133. 10.1002/pros.21228, 2989344, 20717900.
15. Feyerabend S, Stevanovic S, Gouttefangeas C, Wernet D, Hennenlotter J, Bedke J, Dietz K, Pascolo S, Kuczyk M, Rammensee HG, Stenzl A. Novel multi-peptide vaccination in Hla-A2+ hormone sensitive patients with biochemical relapse of prostate cancer. Prostate 2009, 69:917-927. 10.1002/pros.20941, 19267352.
16. Cluff CW. Monophosphoryl lipid A (MPL) as an adjuvant for anti-cancer vaccines: clinical results. Adv Exp Med Biol 2010, 667:111-123.
17. Butler GS, Overall CM. Proteomic identification of multitasking proteins in unexpected locations complicates drug targeting. Nat Rev Drug Discov 2009, 8:935-948. 10.1038/nrd2945, 19949400.
18. Ioannou K, Samara P, Livaniou E, Derhovanessian E, Tsitsilonis OE. Prothymosin alpha: a ubiquitous polypeptide with potential use in cancer diagnosis and therapy. Cancer Immunol Immunother 2012, 61:599-614. 10.1007/s00262-012-1222-8, 22366887.
19. Skopeliti M, Kratzer U, Altenberend F, Panayotou G, Kalbacher H, Stevanovic S, Voelter W, Tsitsilonis OE. Proteomic exploitation on prothymosin alpha-induced mononuclear cell activation. Proteomics 2007, 7:1814-1824. 10.1002/pmic.200600870, 17474146.
20. Mosoian A, Teixeira A, Burns CS, Sander LE, Gusella GL, He C, Blander JM, Klotman P, Klotman ME. Prothymosin-alpha inhibits HIV-1 via Toll-like receptor 4-mediated type I interferon induction. Proc Natl Acad Sci USA 2010, 107:10178-10183. 10.1073/pnas.0914870107, 2890444, 20479248.
21. Skopeliti M, Voutsas IF, Klimentzou P, Tsiatas ML, Beck A, Bamias A, Moraki M, Livaniou E, Neagu M, Voelter W, Tsitsilonis OE. The immunologically active site of prothymosin alpha is located at the carboxy-terminus of the polypeptide. Evaluation of its in vitro effects in cancer patients. Cancer Immunol Immunother 2006, 55:1247-1257. 10.1007/s00262-005-0108-4, 16453152.
22. Baxevanis CN, Thanos D, Reclos GJ, Anastasopoulos E, Tsokos GC, Papamatheakis J, Papamichail M. Prothymosin alpha enhances human and murine MHC class II surface antigen expression and messenger RNA accumulation. J Immunol 1992, 148:1979-1984.
23. Skopeliti M, Iconomidou VA, Derhovanessian E, Pawelec G, Voelter W, Kalbacher H, Hamodrakas SJ, Tsitsilonis OE. Prothymosin alpha immunoactive carboxyl-terminal peptide TKKQKTDEDD stimulates lymphocyte reactions, induces dendritic cell maturation and adopts a beta-sheet conformation in a sequence-specific manner. Mol Immunol 2009, 46:784-792. 10.1016/j.molimm.2008.09.014, 18976813.
24. Kapsenberg ML. Dendritic-cell control of pathogen-driven T-cell polarization. Nat Rev Immunol 2003, 3:984-993. 10.1038/nri1246, 14647480.
25. Hovden AO, Karlsen M, Jonsson R, Appel S. The bacterial preparation OK432 induces IL-12p70 secretion in human dendritic cells in a TLR3 dependent manner. PLoS One 2012, 7:e31217. 10.1371/journal.pone.0031217, 3283639, 22363584.
26. Bevan MJ. Helping the CD8(+) T-cell response. Nat Rev Immunol 2004, 4:595-602. 10.1038/nri1413, 15286726.
27. Rubio V, Stuge TB, Singh N, Betts MR, Weber JS, Roederer M, Lee PP. Ex vivo identification, isolation and analysis of tumor-cytolytic T cells. Nat Med 2003, 9:1377-1382. 10.1038/nm942, 14528297.
28. Darrah PA, Patel DT, De Luca PM, Lindsay RW, Davey DF, Flynn BJ, Hoff ST, Andersen P, Reed SG, Morris SL, Roederer M, Seder RA. Multifunctional TH1 cells define a correlate of vaccine-mediated protection against Leishmania major. Nat Med 2007, 13:843-850. 10.1038/nm1592, 17558415.
29. Precopio ML, Betts MR, Parrino J, Price DA, Gostick E, Ambrozak DR, Asher TE, Douek DC, Harari A, Pantaleo G, Bailer R, Graham BS, Roederer M, Koup RA. Immunization with vaccinia virus induces polyfunctional and phenotypically distinctive CD8(+) T cell responses. J Exp Med 2007, 204:1405-1416. 10.1084/jem.20062363, 2118607, 17535971.
30. Yamamoto M, Akira S. Lipid A receptor TLR4-mediated signaling pathways. Adv Exp Med Biol 2010, 667:59-68.
31. Zanoni I, Ostuni R, Marek LR, Barresi S, Barbalat R, Barton GM, Granucci F, Kagan JC. CD14 controls the LPS-induced endocytosis of Toll-like receptor 4. Cell 2011, 147:868-880. 10.1016/j.cell.2011.09.051, 3217211, 22078883.
32. Nagata A, Takezako N, Tamemoto H, Ohto-Ozaki H, Ohta S, Tominaga S, Yanagisawa K. Soluble ST2 protein inhibits LPS stimulation on monocyte-derived dendritic cells. Cell Mol Immunol 2012, 9:399-409. 10.1038/cmi.2012.29, 22922442.
33. Takeda K, Akira S. TLR signaling pathways. Semin Immunol 2004, 16:3-9. 10.1016/j.smim.2003.10.003, 14751757.
34. Navabi H, Jasani B, Reece A, Clayton A, Tabi Z, Donninger C, Mason M, Adams M. A clinical grade poly I:C-analogue (Ampligen) promotes optimal DC maturation and Th1-type T cell responses of healthy donors and cancer patients in vitro. Vaccine 2009, 27:107-115. 10.1016/j.vaccine.2008.10.024, 18977262.
35. Kalinski P, Edington H, Zeh HJ, Okada H, Butterfield LH, Kirkwood JM, Bartlett DL. Dendritic cells in cancer immunotherapy: vaccines or autologous transplants?. Immunol Res 2011, 50:235-247. 10.1007/s12026-011-8224-z, 3695396, 21717071.
36. Salazar LG, Fikes J, Southwood S, Ishioka G, Knutson KL, Gooley TA, Schiffman K, Disis ML. Immunization of cancer patients with HER-2/neu-derived peptides demonstrating high-affinity binding to multiple class II alleles. Clin Cancer Res 2003, 9:5559-5565.
37. Bernhard H, Salazar L, Schiffman K, Smorlesi A, Schmidt B, Knutson KL, Disis ML. Vaccination against the HER-2/neu oncogenic protein. Endocr Relat Cancer 2002, 9:33-44. 10.1677/erc.0.0090033, 11914181.
38. Green AM, Difazio R, Flynn JL. IFN-γ from CD4 T cells is essential for host survival and enhances CD8 T cell function during Mycobacterium tuberculosis infection. J Immunol 2013, 190:270-277. 10.4049/jimmunol.1200061, 23233724.
39. Almeida JR, Price DA, Papagno L, Arkoub ZA, Sauce D, Bornstein E, Asher TE, Samri A, Schnuriger A, Theodorou I, Costagliola D, Rouzioux C, Agut H, Marcelin AG, Douek D, Autran B, Appay V. Superior control of HIV-1 replication by CD8+ T cells is reflected by their avidity, polyfunctionality, and clonal turnover. J Exp Med 2007, 204:2473-2485. 10.1084/jem.20070784, 2118466, 17893201.
40. Lichtenegger FS, Mueller K, Otte B, Beck B, Hiddemann W, Schendel DJ, Subklewe M. CD86 and IL-12p70 are key players for T helper 1 polarization and natural killer cell activation by Toll-like receptor-induced dendritic cells. PLoS One 2012, 7:e44266. 10.1371/journal.pone.0044266, 3433478, 22962607.
41. Jung ID, Jeong SK, Lee CM, Noh KT, Heo DR, Shin YK, Yun CH, Koh WJ, Akira S, Whang J, Kim HJ, Park WS, Shin SJ, Park YM. Enhanced efficacy of therapeutic cancer vaccines produced by co-treatment with Mycobacterium tuberculosis heparin-binding hemagglutinin, a novel TLR4 agonist. Cancer Res 2011, 71:2858-2870. 10.1158/0008-5472.CAN-10-3487, 21368092.
42. Baxevanis CN, Voutsas IF, Tsitsilonis OE. Toll-like receptor agonists: current status and future perspective on their utility as adjuvants in improving anticancer vaccination strategies. Immunotherapy 2013, 5:497-511. 10.2217/imt.13.24, 23638745.
43. Bianchi ME. DAMPs, PAMPs and alarmins: all we need to know about danger. J Leukoc Biol 2007, 81:1-5.
44. Messmer D, Yang H, Telusma G, Knoll F, Li J, Messmer B, Tracey KJ, Chiorazzi N. High mobility group box protein 1: an endogenous signal for dendritic cell maturation and Th1 polarization. J Immunol 2004, 173:307-313.
45. Saenz R, Souza Cda S, Huang CT, Larsson M, Esener S, Messmer D. HMGB1-derived peptide acts as adjuvant inducing immune responses to peptide and protein antigen. Vaccine 2010, 28:7556-7562. 10.1016/j.vaccine.2010.08.054, 2963688, 20800114.
46. Wang Y, Kelly CG, Singh M, McGowan EG, Carrara AS, Bergmeier LA, Lehner T. Stimulation of Th1-polarizing cytokines, C-C chemokines, maturation of dendritic cells, and adjuvant function by the peptide binding fragment of heat shock protein 70. J Immunol 2002, 169:2422-2429.
47. Wu Y, Wan T, Zhou X, Wang B, Yang F, Li N, Chen G, Dai S, Liu S, Zhang M, Cao X. Hsp70-like protein 1 fusion protein enhances induction of carcinoembryonic antigen-specific CD8+ CTL response by dendritic cell vaccine. Cancer Res 2005, 65:4947-4954. 10.1158/0008-5472.CAN-04-3912, 15930317.
48. Tewary P, Yang D, de la Rosa G, Li Y, Finn MW, Krensky AM, Clayberger C, Oppenheim JJ. Granulysin activates antigen-presenting cells through TLR4 and acts as an immune alarmin. Blood 2010, 116:3465-3474. 10.1182/blood-2010-03-273953, 2981473, 20660289.
49. Cordero OJ, Sarandeses C, López-Rodríguez JL, Nogueira M. The presence and cytotoxicity of CD16+ CD2- subset from PBL and NK cells in long-term IL-2 cultures enhanced by Prothymosin-alpha. Immunopharmacology 1995, 29:215-223. 10.1016/0162-3109(95)00057-Z, 7542644.
50. Eckert K, Grünberg E, Garbin F, Maurer HR. Preclinical studies with prothymosin alpha1 on mononuclear cells from tumor patients. Int J Immunopharmacol 1997, 19:493-500. 10.1016/S0192-0561(97)00079-9, 9637344.
51. Baxevanis CN, Gritzapis AD, Spanakos G, Tsitsilonis OE, Papamichail M. Induction of tumor-specific T lymphocyte responses in vivo by prothymosin alpha. Cancer Immunol Immunother 1995, 40:410-418. 10.1007/BF01525392, 7543022.
52. Voutsas IF, Baxevanis CN, Gritzapis AD, Missitzis I, Stathopoulos GP, Archodakis G, Banis C, Voelter W, Papamichail M. Synergy between interleukin-2 and prothymosin alpha for the increased generation of cytotoxic T lymphocytes against autologous human carcinomas. Cancer Immunol Immunother 2000, 49:449-458. 10.1007/s002620000132, 11043852.
53. Telusma G, Datta S, Mihajlov I, Ma W, Li J, Yang H, Newman W, Messmer BT, Minev B, Schmidt-Wolf IG, Tracey KJ, Chiorazzi N, Messmer D. Dendritic cell activating peptides induce distinct cytokine profiles. Int Immunol 2006, 18:1563-1573. 10.1093/intimm/dxl089, 16966494.
54. Park JS, Svetkauskaite D, He Q, Kim JY, Strassheim D, Ishizaka A, Abraham E. Involvement of toll-like receptors 2 and 4 in cellular activation by high mobility group box 1 protein. J Biol Chem 2004, 279:7370-7377.
55. Park JS, Gamboni-Robertson F, He Q, Svetkauskaite D, Kim JY, Strassheim D, Sohn JW, Yamada S, Maruyama I, Banerjee A, Ishizaka A, Abraham E. High mobility group box 1 protein interacts with multiple Toll-like receptors. Am J Physiol Cell Physiol 2006, 290:C917-924.
56. Yu M, Wang H, Ding A, Golenbock DT, Latz E, Czura CJ, Fenton MJ, Tracey KJ, Yang H. HMGB1 signals through toll-like receptor (TLR) 4 and TLR2. Shock 2006, 26:174-179. 10.1097/01.shk.0000225404.51320.82, 16878026.
57. Roelofs MF, Boelens WC, Joosten LA, Abdollahi-Roodsaz S, Geurts J, Wunderink LU, Schreurs BW, van den Berg WB, Radstake TR. Identification of small heat shock protein B8 (HSP22) as a novel TLR4 ligand and potential involvement in the pathogenesis of rheumatoid arthritis. J Immunol 2006, 176:7021-7027.
58. Vabulas RM, Ahmad-Nejad P, da Costa C, Miethke T, Kirschning CJ, Häcker H, Wagner HL. Endocytosed HSP60s use toll-like receptor 2 (TLR2) and TLR4 to activate the toll/interleukin-1 receptor signaling pathway in innate immune cells. J Biol Chem 2001, 276:31332-31339. 10.1074/jbc.M103217200, 11402040.
59. Vabulas RM, Ahmad-Nejad P, Ghose S, Kirschning CJ, Issels RD, Wagner H. HSP70 as endogenous stimulus of the Toll/interleukin-1 receptor signal pathway. J Biol Chem 2002, 277:15107-15112. 10.1074/jbc.M111204200, 11842086.
60. Jiang XX, Zhang Y, Liu B, Zhang SX, Wu Y, Yu XD, Mao N. Human mesenchymal stem cells inhibit differentiation and function of monocyte-derived dendritic cells. Blood 2005, 105:4120-4126. 10.1182/blood-2004-02-0586, 15692068.
61. Jarnjak-Jankovic S, Hammerstad H, Saebøe-Larssen S, Kvalheim G, Gaudernack G. A full scale comparative study of methods for generation of functional dendritic cells for use as cancer vaccines. BMC Cancer 2007, 7:119. 10.1186/1471-2407-7-119, 1931601, 17608923.
62. Zanoni I, Granucci F. Differences in lipopolysaccharide-induced signaling between conventional dendritic cells and macrophages. Immunobiology 2010, 215:709-712. 10.1016/j.imbio.2010.05.026, 20579765.
63. Bosisio D, Polentarutti N, Sironi M, Bernasconi S, Miyake K, Webb GR, Martin MU, Mantovani A, Muzio M. Stimulation of toll-like receptor 4 expression in human mononuclear phagocytes by interferon-gamma: a molecular basis for priming and synergism with bacterial lipopolysaccharide. Blood 2002, 99:3427-3431. 10.1182/blood.V99.9.3427, 11964313.
64. Robbins PF. Tumor associated antigens. Analyzing T cell responses 2005, 9-42. Netherlands: Springer, Nagorsen D, Marincola FM.
65. Gavalas NG, Tsiatas M, Tsitsilonis O, Politi E, Ioannou K, Ziogas AC, Rodolakis A, Vlahos G, Thomakos N, Haidopoulos D, Terpos E, Antsaklis A, Dimopoulos MA, Bamias A. VEGF directly suppresses activation of T cells from ascites secondary to ovarian cancer via VEGF receptor type 2. Br J Cancer 2012, 107:1869-1875. 10.1038/bjc.2012.468, 23169339.
66. Sun Y, Stevanovic S, Song M, Schwantes A, Kirkpatrick CJ, Schadendorf D, Cichutek K. The kinase insert domain-containing receptor is an angiogenesis-associated antigen recognized by human cytotoxic T lymphocytes. Blood 2006, 107:1476-1483. 10.1182/blood-2005-05-1912, 16234362.
67. Antonelou MH, Kriebardis AG, Stamoulis KE, Trougakos IP, Papassideri IS. Apolipoprotein J/clusterin in human erythrocytes is involved in the molecular process of defected material disposal during vesiculation. PLoS One 2011, 6:e26033. 10.1371/journal.pone.0026033, 3189238, 22016805.