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01-02-2017 | Original Article

Oncolysate-loaded Escherichia coli bacterial ghosts enhance the stimulatory capacity of human dendritic cells

Authors: Jaroslav Michalek, Renata Hezova, Pavlina Turanek-Knötigova, Jana Gabkova, Marius Strioga, Werner Lubitz, Pavol Kudela

Published in: Cancer Immunology, Immunotherapy | Issue 2/2017

Abstract

The natural adjuvant properties of bacterial ghosts (BGs) lie within the presence of intact pathogen-associated molecular patterns on their surface. BGs can improve the direct delivery, natural processing and presentation of target antigens within dendritic cells (DCs). Moreover, sensitization of human DCs by cancer cell lysate (oncolysate)-loaded BGs in the presence of IFN-α and GM-CSF enhanced DC maturation as indicated by an increased expression of maturation markers and co-stimulatory molecules, higher production of IL-12p70 and stimulation of significantly increased proliferation of both autologous CD4⁺ and CD8⁺ T cells compared to DCs matured in the presence of purified lipopolysaccharide. The induced T cells efficiently recognized oncolysate-derived tumor-associated antigens expressed by cancer cells used for the production of oncolysate. Our optimized one-step simultaneous antigen delivery and DC maturation-inducing method emerges as a promising tool for the development and implementation of next-generation cellular cancer immunotherapies.

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Stewart BW, Wild CP (eds) (2014) World cancer report 2014. International agency for research on cancer, Lyon, France

Chen G, Emens LA (2013) Chemoimmunotherapy: reengineering tumor immunity. Cancer Immunol Immunother 62(2):203–216. doi:10.1007/s00262-012-1388-0 CrossRefPubMedPubMedCentral

Vanneman M, Dranoff G (2012) Combining immunotherapy and targeted therapies in cancer treatment. Nat Rev Cancer 12(4):237–251. doi:10.1038/nrc3237 CrossRefPubMedPubMedCentral

Bhatia A, Kumar Y (2014) Cellular and molecular mechanisms in cancer immune escape: a comprehensive review. Expert Rev Clin Immunol 10(1):41–62. doi:10.1586/1744666X.2014.865519 CrossRefPubMed

Zitvogel L, Galluzzi L, Smyth MJ, Kroemer G (2013) Mechanism of action of conventional and targeted anticancer therapies: reinstating immunosurveillance. Immunity 39(1):74–88. doi:10.1016/j.immuni.2013.06.014 CrossRefPubMed

Nguyen T, Urban J, Kalinski P (2014) Therapeutic cancer vaccines and combination immunotherapies involving vaccination. Immunotargets Ther 3:135–150. doi:10.2147/ITT.S40264 PubMedPubMedCentral

Schijns V, Tartour E, Michalek J, Stathopoulos A, Dobrovolskiene NT, Strioga MM (2014) Immune adjuvants as critical guides directing immunity triggered by therapeutic cancer vaccines. Cytotherapy 16(4):427–439. doi:10.1016/j.jcyt.2013.09.008 CrossRefPubMed

Palucka K, Banchereau J (2013) Dendritic-cell-based therapeutic cancer vaccines. Immunity 39(1):38–48. doi:10.1016/j.immuni.2013.07.004 CrossRefPubMedPubMedCentral

Strioga MM, Felzmann T, Powell DJ Jr, Ostapenko V, Dobrovolskiene NT, Matuskova M, Michalek J, Schijns VE (2013) Therapeutic dendritic cell-based cancer vaccines: the state of the art. Crit Rev Immunol 33(6):489–547. doi:10.1615/CritRevImmunol.2013008033 CrossRefPubMed

10.

Kantoff PW, Higano CS, Shore ND, Berger ER, Small EJ, Penson DF, Redfern CH, Ferrari AC, Dreicer R, Sims RB, Xu Y, Frohlich MW, Schellhammer PF (2010) Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N Engl J Med 363(5):411–422. doi:10.1056/NEJMoa1001294 CrossRefPubMed

11.

Butterfield LH (2013) Dendritic cells in cancer immunotherapy clinical trials: are we making progress? Front Immunol 4:454. doi:10.3389/fimmu.2013.00454 CrossRefPubMedPubMedCentral

12.

Anguille S, Smits EL, Lion E, van Tendeloo VF, Berneman ZN (2014) Clinical use of dendritic cells for cancer therapy. Lancet Oncol 15(7):e257–e267. doi:10.1016/S1470-2045(13)70585-0 CrossRefPubMed

13.

Datta J, Terhune JH, Lowenfeld L, Cintolo JA, Xu S, Roses RE, Czerniecki BJ (2014) Optimizing dendritic cell-based approaches for cancer immunotherapy. Yale J Biol Med 87(4):491–518PubMedPubMedCentral

14.

Mailliard RB, Wankowicz-Kalinska A, Cai Q, Wesa A, Hilkens CM, Kapsenberg ML, Kirkwood JM, Storkus WJ, Kalinski P (2004) Alpha-type-1 polarized dendritic cells: a novel immunization tool with optimized CTL-inducing activity. Cancer Res 64(17):5934–5937. doi:10.1158/0008-5472.CAN-04-1261 CrossRefPubMed

15.

Lee MKt, Xu S, Fitzpatrick EH, Sharma A, Graves HL, Czerniecki BJ (2013) Inhibition of CD4⁺ CD25⁺ regulatory T cell function and conversion into Th1-like effectors by a Toll-like receptor-activated dendritic cell vaccine. PLoS ONE 8(11):e74698. doi:10.1371/journal.pone.0074698 CrossRefPubMedPubMedCentral

16.

Vopenkova K, Mollova K, Buresova I, Michalek J (2012) Complex evaluation of human monocyte-derived dendritic cells for cancer immunotherapy. J Cell Mol Med 16(11):2827–2837. doi:10.1111/j.1582-4934.2012.01614.x CrossRefPubMedPubMedCentral

17.

Sundarasetty BS, Chan L, Darling D, Giunti G, Farzaneh F, Schenck F, Naundorf S, Kuehlcke K, Ruggiero E, Schmidt M, von Kalle C, Rothe M, Hoon DS, Gerasch L, Figueiredo C, Koehl U, Blasczyk R, Gutzmer R, Stripecke R (2015) Lentivirus-induced ‘Smart’ dendritic cells: pharmacodynamics and GMP-compliant production for immunotherapy against TRP2-positive melanoma. Gene Ther 22(9):707–720. doi:10.1038/gt.2015.43 CrossRefPubMedPubMedCentral

18.

Powell KL, Stephens AS, Ralph SJ (2015) Development of a potent melanoma vaccine capable of stimulating CD8(+) T-cells independently of dendritic cells in a mouse model. Cancer Immunol Immunother 64(7):861–872. doi:10.1007/s00262-015-1695-3 CrossRefPubMed

19.

Muhammad A, Champeimont J, Mayr UB, Lubitz W, Kudela P (2012) Bacterial ghosts as carriers of protein subunit and DNA-encoded antigens for vaccine applications. Expert Rev Vaccines 11(1):97–116. doi:10.1586/erv.11.149 CrossRefPubMed

20.

Ebensen T, Paukner S, Link C, Kudela P, de Domenico C, Lubitz W, Guzman CA (2004) Bacterial ghosts are an efficient delivery system for DNA vaccines. J Immunol 172(11):6858–6865. doi:10.4049/jimmunol.172.11.6858 CrossRefPubMed

21.

Kudela P, Paukner S, Mayr UB, Cholujova D, Schwarczova Z, Sedlak J, Bizik J, Lubitz W (2005) Bacterial ghosts as novel efficient targeting vehicles for DNA delivery to the human monocyte-derived dendritic cells. J Immunother 28(2):136–143CrossRefPubMed

22.

Kudela P, Schwarczova Z, Sedlak J, Bizik J (2001) Conditioned medium from HeLa cells enhances motility of human monocyte-derived dendritic cells but abrogates their maturation and endocytic activity. Neoplasma 48(5):382–388PubMed

23.

Ma Y, Shurin GV, Peiyuan Z, Shurin MR (2013) Dendritic cells in the cancer microenvironment. J Cancer 4(1):36–44. doi:10.7150/jca.5046 CrossRefPubMed

24.

Langemann T, Koller VJ, Muhammad A, Kudela P, Mayr UB, Lubitz W (2010) The bacterial ghost platform system: production and applications. Bioeng Bugs 1(5):326–336. doi:10.4161/bbug.1.5.12540 CrossRefPubMedPubMedCentral

25.

Jonuleit H, Kuhn U, Muller G, Steinbrink K, Paragnik L, Schmitt E, Knop J, Enk AH (1997) Pro-inflammatory cytokines and prostaglandins induce maturation of potent immunostimulatory dendritic cells under fetal calf serum-free conditions. Eur J Immunol 27(12):3135–3142. doi:10.1002/eji.1830271209 CrossRefPubMed

26.

Kalinski P (2012) Regulation of immune responses by prostaglandin E2. J Immunol 188(1):21–28. doi:10.4049/jimmunol.1101029 CrossRefPubMedPubMedCentral

27.

Witte A, Wanner G, Sulzner M, Lubitz W (1992) Dynamics of PhiX174 protein E-mediated lysis of Escherichia coli. Arch Microbiol 157(4):381–388CrossRefPubMed

28.

Eko FO, Mania-Pramanik J, Pais R, Pan Q, Okenu DM, Johnson A, Ibegbu C, He C, He Q, Russell R, Black CM, Igietseme JU (2014) Vibrio cholerae ghosts (VCG) exert immunomodulatory effect on dendritic cells for enhanced antigen presentation and induction of protective immunity. BMC Immunol 15(1):584. doi:10.1186/s12865-014-0056-x CrossRefPubMedPubMedCentral

29.

Kudela P, Paukner S, Mayr UB, Cholujova D, Kohl G, Schwarczova Z, Bizik J, Sedlak J, Lubitz W (2008) Effective gene transfer to melanoma cells using bacterial ghosts. Cancer Lett 262(1):54–63. doi:10.1016/j.canlet.2007.11.031 CrossRefPubMed

30.

Paukner S, Kudela P, Kohl G, Schlapp T, Friedrichs S, Lubitz W (2005) DNA-loaded bacterial ghosts efficiently mediate reporter gene transfer and expression in macrophages. Mol Ther 11(2):215–223. doi:10.1016/j.ymthe.2004.09.024 CrossRefPubMed

31.

de Rosa F, Ridolfi L, Ridolfi R, Gentili G, Valmorri L, Nanni O, Petrini M, Fiammenghi L, Granato AM, Ancarani V, Pancisi E, Soldati V, Cassan S, Riccobon A, Parisi E, Romeo A, Turci L, Guidoboni M (2014) Vaccination with autologous dendritic cells loaded with autologous tumor lysate or homogenate combined with immunomodulating radiotherapy and/or preleukapheresis IFN-alpha in patients with metastatic melanoma: a randomised “proof-of-principle” phase II study. J Transl Med 12:209. doi:10.1186/1479-5876-12-209 CrossRefPubMedPubMedCentral

32.

Eyrich M, Schreiber SC, Rachor J, Krauss J, Pauwels F, Hain J, Wolfl M, Lutz MB, de Vleeschouwer S, Schlegel PG, Van Gool SW (2014) Development and validation of a fully GMP-compliant production process of autologous, tumor-lysate-pulsed dendritic cells. Cytotherapy 16(7):946–964. doi:10.1016/j.jcyt.2014.02.017 CrossRefPubMed

33.

Gonzalez FE, Ortiz C, Reyes M, Dutzan N, Patel V, Pereda C, Gleisner MA, Lopez MN, Gutkind JS, Salazar-Onfray F (2014) Melanoma cell lysate induces CCR7 expression and in vivo migration to draining lymph nodes of therapeutic human dendritic cells. Immunology 142(3):396–405. doi:10.1111/imm.12264 CrossRefPubMedPubMedCentral

34.

Chiang CL, Kandalaft LE, Tanyi J, Hagemann AR, Motz GT, Svoronos N, Montone K, Mantia-Smaldone GM, Smith L, Nisenbaum HL, Levine BL, Kalos M, Czerniecki BJ, Torigian DA, Powell DJ Jr, Mick R, Coukos G (2013) A dendritic cell vaccine pulsed with autologous hypochlorous acid-oxidized ovarian cancer lysate primes effective broad antitumor immunity: from bench to bedside. Clin Cancer Res 19(17):4801–4815. doi:10.1158/1078-0432.CCR-13-1185 CrossRefPubMedPubMedCentral

35.

Truxova I, Pokorna K, Kloudova K, Partlova S, Spisek R, Fucikova J (2014) Day 3 Poly (I:C)-activated dendritic cells generated in CellGro for use in cancer immunotherapy trials are fully comparable to standard Day 5 DCs. Immunol Lett 160(1):39–49. doi:10.1016/j.imlet.2014.03.010 CrossRefPubMed

36.

Win SJ, McMillan DG, Errington-Mais F, Ward VK, Young SL, Baird MA, Melcher AA (2012) Enhancing the immunogenicity of tumour lysate-loaded dendritic cell vaccines by conjugation to virus-like particles. Br J Cancer 106(1):92–98. doi:10.1038/bjc.2011.538 CrossRefPubMed

37.

Schreiber H, Rowley JD, Rowley DA (2011) Targeting mutations predictably. Blood 118(4):830–831. doi:10.1182/blood-2011-06-357541 CrossRefPubMed

38.

Lakshminarayanan V, Supekar NT, Wei J, McCurry DB, Dueck AC, Kosiorek HE, Trivedi PP, Bradley JM, Madsen CS, Pathangey LB, Hoelzinger DB, Wolfert MA, Boons GJ, Cohen PA, Gendler SJ (2016) MUC1 vaccines, comprised of glycosylated or non-glycosylated peptides or tumor-derived MUC1, can circumvent immunoediting to control tumor growth in MUC1 transgenic mice. PLoS ONE 11(1):e0145920. doi:10.1371/journal.pone.0145920 CrossRefPubMedPubMedCentral

39.

Nicholaou T, Chen W, Davis ID, Jackson HM, Dimopoulos N, Barrow C, Browning J, Macgregor D, Williams D, Hopkins W, Maraskovsky E, Venhaus R, Pan L, Hoffman EW, Old LJ, Cebon J (2011) Immunoediting and persistence of antigen-specific immunity in patients who have previously been vaccinated with NY-ESO-1 protein formulated in ISCOMATRIX. Cancer Immunol Immunother 60(11):1625–1637. doi:10.1007/s00262-011-1041-3 CrossRefPubMed

40.

Berard F, Blanco P, Davoust J, Neidhart-Berard EM, Nouri-Shirazi M, Taquet N, Rimoldi D, Cerottini JC, Banchereau J, Palucka AK (2000) Cross-priming of naive CD8 T cells against melanoma antigens using dendritic cells loaded with killed allogeneic melanoma cells. J Exp Med 192(11):1535–1544CrossRefPubMedPubMedCentral

41.

Neidhardt-Berard EM, Berard F, Banchereau J, Palucka AK (2004) Dendritic cells loaded with killed breast cancer cells induce differentiation of tumor-specific cytotoxic T lymphocytes. Breast Cancer Res 6(4):R322–R328. doi:10.1186/bcr794 CrossRefPubMedPubMedCentral

42.

Aguilar LK, Guzik BW, Aguilar-Cordova E (2011) Cytotoxic immunotherapy strategies for cancer: mechanisms and clinical development. J Cell Biochem 112(8):1969–1977. doi:10.1002/jcb.23126 CrossRefPubMed

43.

Baxevanis CN, Voutsas IF, Tsitsilonis OE, Gritzapis AD, Sotiriadou R, Papamichail M (2000) Tumor-specific CD4⁺ T lymphocytes from cancer patients are required for optimal induction of cytotoxic T cells against the autologous tumor. J Immunol 164(7):3902–3912CrossRefPubMed

44.

Quezada SA, Simpson TR, Peggs KS, Merghoub T, Vider J, Fan X, Blasberg R, Yagita H, Muranski P, Antony PA, Restifo NP, Allison JP (2010) Tumor-reactive CD4⁺ T cells develop cytotoxic activity and eradicate large established melanoma after transfer into lymphopenic hosts. J Exp Med 207(3):637–650. doi:10.1084/jem.20091918 CrossRefPubMedPubMedCentral

45.

Aarntzen EH, De Vries IJ, Lesterhuis WJ, Schuurhuis D, Jacobs JF, Bol K, Schreibelt G, Mus R, De Wilt JH, Haanen JB, Schadendorf D, Croockewit A, Blokx WA, Van Rossum MM, Kwok WW, Adema GJ, Punt CJ, Figdor CG (2013) Targeting CD4+ T-helper cells improves the induction of antitumor responses in dendritic cell-based vaccination. Cancer Res 73(1):19–29. doi:10.1158/0008-5472.CAN-12-1127 CrossRefPubMed

46.

Trombetta ES, Ebersold M, Garrett W, Pypaert M, Mellman I (2003) Activation of lysosomal function during dendritic cell maturation. Science 299(5611):1400–1403. doi:10.1126/science.1080106 CrossRefPubMed

47.

Spadaro F, Lapenta C, Donati S, Abalsamo L, Barnaba V, Belardelli F, Santini SM, Ferrantini M (2012) IFN-alpha enhances cross-presentation in human dendritic cells by modulating antigen survival, endocytic routing, and processing. Blood 119(6):1407–1417. doi:10.1182/blood-2011-06-363564 CrossRefPubMed

48.

Berk E, Xu S, Czerniecki BJ (2014) Dendritic cells matured in the presence of TLR ligands overcome the immunosuppressive functions of regulatory T cells. Oncoimmunology 3:e27617. doi:10.4161/onci.27617 CrossRefPubMedPubMedCentral

49.

Brezar V, Ruffin N, Richert L, Surenaud M, Lacabaratz C, Palucka K, Thiebaut R, Banchereau J, Levy Y, Seddiki N (2015) Decreased HIV-specific T-regulatory responses are associated with effective DC-vaccine induced immunity. PLoS Pathog 11(3):e1004752. doi:10.1371/journal.ppat.1004752 CrossRefPubMedPubMedCentral

50.

Santini SM, Lapenta C, Santodonato L, D’Agostino G, Belardelli F, Ferrantini M (2009) IFN-alpha in the generation of dendritic cells for cancer immunotherapy. Handb Exp Pharmacol 188:295–317. doi:10.1007/978-3-540-71029-5_14 CrossRef

51.

Pantel A, Teixeira A, Haddad E, Wood EG, Steinman RM, Longhi MP (2014) Direct type I IFN but not MDA5/TLR3 activation of dendritic cells is required for maturation and metabolic shift to glycolysis after poly IC stimulation. PLoS Biol 12(1):e1001759. doi:10.1371/journal.pbio.1001759 CrossRefPubMedPubMedCentral

Title: Oncolysate-loaded Escherichia coli bacterial ghosts enhance the stimulatory capacity of human dendritic cells
Authors: Jaroslav Michalek
Renata Hezova
Pavlina Turanek-Knötigova
Jana Gabkova
Marius Strioga
Werner Lubitz
Pavol Kudela
Publication date: 01-02-2017
Publisher: Springer Berlin Heidelberg
Published in: Cancer Immunology, Immunotherapy / Issue 2/2017
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-016-1932-4

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