Novel metronomic chemotherapy and cancer vaccine combinatorial strategy for hepatocellular carcinoma in a mouse model

Cancer Immunology, Immunotherapy

Volumn 64, Issue 10, 2015, Pages 1305-1314

  Tagliamonte, Maria ^a   Petrizzo, Annacarmen ^a   Napolitano, Maria ^a   Luciano, Antonio ^a   Arra, Claudio ^a   Maiolino, Piera ^a   Izzo, Francesco ^a   Tornesello, Maria Lina ^a   Aurisicchio, Luigi ^b   Ciliberto, Gennaro ^a   Buonaguro, Franco M ^a   Buonaguro, Luigi ^a  

^a NATIONAL CANCER INSTITUTE   (Italy)

^b Laboratory of Clinical Immunology Istituto Nazionale per lo Studio e la Cura dei Tumori “Fondazione Pascale” IRCCS ^*  (Italy)

Author keywords

Cancer vaccine; Combinatorial strategy; Immunotherapy; Liver cancer; Metronomic chemotherapy; PIVAC 14

Indexed keywords

CANCER VACCINE; CORE PROTEIN; CYCLOPHOSPHAMIDE; DOCETAXEL; EPITOPE; HEPATITIS C ANTIGEN; IMMUNOLOGICAL ADJUVANT; NONSTRUCTURAL PROTEIN 3; PACLITAXEL; TELOMERASE REVERSE TRANSCRIPTASE; TRANSCRIPTION FACTOR FOXP3; TUMOR ANTIGEN; ALKYLATING AGENT; ANTINEOPLASTIC AGENT; TAXOID; TELOMERASE; TERT PROTEIN, MOUSE; VIRUS ANTIGEN;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANTIGEN SPECIFICITY; CANCER COMBINATION CHEMOTHERAPY; CANCER IMMUNOTHERAPY; CD4+ CD25+ T LYMPHOCYTE; CD8+ T LYMPHOCYTE; CELLULAR IMMUNITY; CONTROLLED STUDY; DRUG MEGADOSE; HEPATITIS C VIRUS; LIVER CELL CARCINOMA; LOW DRUG DOSE; METRONOMIC DRUG ADMINISTRATION; MONOTHERAPY; MOUSE; NONHUMAN; PRIORITY JOURNAL; REGULATORY T LYMPHOCYTE; REVIEW; T LYMPHOCYTE SUBPOPULATION; TUMOR IMMUNITY; ANIMAL; C57BL MOUSE; CARCINOMA, HEPATOCELLULAR; CELL CULTURE; COMPLICATION; DISEASE MODEL; FEMALE; HEPACIVIRUS; HEPATITIS B; HEPATITIS B VIRUS; HEPATITIS C; HUMAN; IMMUNOLOGY; LIVER NEOPLASMS; LYMPHOCYTE ACTIVATION; MALE; METABOLISM; MULTIMODALITY CANCER THERAPY;

ADMINISTRATION, METRONOMIC; ALKYLATING AGENTS; ANIMALS; ANTIGENS, VIRAL; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; CANCER VACCINES; CARCINOMA, HEPATOCELLULAR; CELLS, CULTURED; COMBINED MODALITY THERAPY; DISEASE MODELS, ANIMAL; FEMALE; HEPACIVIRUS; HEPATITIS B; HEPATITIS B VIRUS; HEPATITIS C; HUMANS; IMMUNODOMINANT EPITOPES; LIVER NEOPLASMS; LYMPHOCYTE ACTIVATION; MALE; MICE, INBRED C57BL; T-LYMPHOCYTE SUBSETS; T-LYMPHOCYTES, REGULATORY; TAXOIDS; TELOMERASE;

EID: 84940720866     PISSN: 03407004     EISSN: 14320851     Source Type: Journal    
DOI: 10.1007/s00262-015-1698-0     Document Type: Review

References (69)

1. McGlynn KA, London WT (2011) The global epidemiology of hepatocellular carcinoma: present and future. Clin Liver Dis 15:223–243
2. Franceschi S, Raza SA (2009) Epidemiology and prevention of hepatocellular carcinoma. Cancer Lett 286:5–8
3. Parkin DM (2006) The global health burden of infection-associated cancers in the year 2002. Int J Cancer 118:3030–3044
4. La Vecchia C, Negri E, Cavalieri DL, Franceschi S (1998) Liver cirrhosis and the risk of primary liver cancer. Eur J Cancer Prev 7:315–320
5. Moriya K, Fujie H, Shintani Y, Yotsuyanagi H, Tsutsumi T, Ishibashi K, Matsuura Y, Kimura S, Miyamura T, Koike K (1998) The core protein of hepatitis C virus induces hepatocellular carcinoma in transgenic mice. Nat Med 4:1065–1067
6. Anzola M (2004) Hepatocellular carcinoma: role of hepatitis B and hepatitis C viruses proteins in hepatocarcinogenesis. J Viral Hepat 11:383–393
7. Schwartz M, Dvorchik I, Roayaie S, Fiel MI, Finkelstein S, Marsh JW, Martignetti JA, Llovet JM (2008) Liver transplantation for hepatocellular carcinoma: extension of indications based on molecular markers. J Hepatol 49:581–588
8. Mazzaferro V, Llovet JM, Miceli R, Bhoori S, Schiavo M, Mariani L, Camerini T, Roayaie S, Schwartz ME, Grazi GL, Adam R, Neuhaus P, Salizzoni M, Bruix J, Forner A, De CL, Cillo U, Burroughs AK, Troisi R, Rossi M, Gerunda GE, Lerut J, Belghiti J, Boin I, Gugenheim J, Rochling F, Van HB, Majno P (2009) Predicting survival after liver transplantation in patients with hepatocellular carcinoma beyond the Milan criteria: a retrospective, exploratory analysis. Lancet Oncol 10:35–43
9. Llovet JM, Bruix J (2008) Novel advancements in the management of hepatocellular carcinoma in 2008. J Hepatol 48(Suppl 1):S20–S37
10. Lencioni R, Crocetti L (2012) Local-regional treatment of hepatocellular carcinoma. Radiology 262:43–58
11. Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc JF, de Oliveira AC, Santoro A, Raoul JL, Forner A, Schwartz M, Porta C, Zeuzem S, Bolondi L, Greten TF, Galle PR, Seitz JF, Borbath I, Haussinger D, Giannaris T, Shan M, Moscovici M, Voliotis D, Bruix J (2008) Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 359:378–390
12. Reinisch W, Holub M, Katz A, Herneth A, Lichtenberger C, Schoniger-Hekele M, Waldhoer T, Oberhuber G, Ferenci P, Gangl A, Mueller C (2002) Prospective pilot study of recombinant granulocyte-macrophage colony-stimulating factor and interferon-gamma in patients with inoperable hepatocellular carcinoma. J Immunother 25:489–499
13. Sangro B, Mazzolini G, Ruiz J, Herraiz M, Quiroga J, Herrero I, Benito A, Larrache J, Pueyo J, Subtil JC, Olague C, Sola J, Sadaba B, Lacasa C, Melero I, Qian C, Prieto J (2004) Phase I trial of intratumoral injection of an adenovirus encoding interleukin-12 for advanced digestive tumors. J Clin Oncol 22:1389–1397
14. Shi M, Zhang B, Tang ZR, Lei ZY, Wang HF, Feng YY, Fan ZP, Xu DP, Wang FS (2004) Autologous cytokine-induced killer cell therapy in clinical trial phase I is safe in patients with primary hepatocellular carcinoma. World J Gastroenterol 10:1146–1151
15. Takayama T, Sekine T, Makuuchi M, Yamasaki S, Kosuge T, Yamamoto J, Shimada K, Sakamoto M, Hirohashi S, Ohashi Y, Kakizoe T (2000) Adoptive immunotherapy to lower postsurgical recurrence rates of hepatocellular carcinoma: a randomised trial. Lancet 356:802–807
16. Butterfield LH, Ribas A, Dissette VB, Lee Y, Yang JQ, De la RP, Duran SD, Hernandez J, Seja E, Potter DM, McBride WH, Finn R, Glaspy JA, Economou JS (2006) A phase I/II trial testing immunization of hepatocellular carcinoma patients with dendritic cells pulsed with four alpha-fetoprotein peptides. Clin Cancer Res 12:2817–2825
17. Butterfield LH, Ribas A, Meng WS, Dissette VB, Amarnani S, Vu HT, Seja E, Todd K, Glaspy JA, McBride WH, Economou JS (2003) T-cell responses to HLA-A*0201 immunodominant peptides derived from alpha-fetoprotein in patients with hepatocellular cancer. Clin Cancer Res 9:5902–5908
18. Lee WC, Wang HC, Hung CF, Huang PF, Lia CR, Chen MF (2005) Vaccination of advanced hepatocellular carcinoma patients with tumor lysate-pulsed dendritic cells: a clinical trial. J Immunother 28:496–504
19. Palmer DH, Midgley RS, Mirza N, Torr EE, Ahmed F, Steele JC, Steven NM, Kerr DJ, Young LS, Adams DH (2009) A phase II study of adoptive immunotherapy using dendritic cells pulsed with tumor lysate in patients with hepatocellular carcinoma. Hepatology 49:124–132
20. Buonaguro L, Petrizzo A, Tagliamonte M, Tornesello ML, Buonaguro FM (2013) Challenges in cancer vaccine development for hepatocellular carcinoma. J Hepatol 59:897–903
21. Buonaguro L, Petrizzo A, Tornesello ML, Buonaguro FM (2011) Translating tumor antigens into cancer vaccines. Clin Vaccine Immunol 18:23–34
22. Kim NW, Piatyszek MA, Prowse KR, Harley CB, West MD, Ho PL, Coviello GM, Wright WE, Weinrich SL, Shay JW (1994) Specific association of human telomerase activity with immortal cells and cancer. Science 266:2011–2015
23. Hiyama E, Hiyama K (2003) Telomerase as tumor marker. Cancer Lett 194:221–233
24. Hastie ND, Dempster M, Dunlop MG, Thompson AM, Green DK, Allshire RC (1990) Telomere reduction in human colorectal carcinoma and with ageing. Nature 346:866–868
25. Nault JC, Mallet M, Pilati C, Calderaro J, Bioulac-Sage P, Laurent C, Laurent A, Cherqui D, Balabaud C, Zucman-Rossi J (2013) High frequency of telomerase reverse-transcriptase promoter somatic mutations in hepatocellular carcinoma and preneoplastic lesions. Nat Commun 4:2218
26. Cevik D, Yildiz G, Ozturk M (2015) Common telomerase reverse transcriptase promoter mutations in hepatocellular carcinomas from different geographical locations. World J Gastroenterol 21:311–317
27. Harley CB (2008) Telomerase and cancer therapeutics. Nat Rev Cancer 8:167–179
28. Shaw VE, Naisbitt DJ, Costello E, Greenhalf W, Park BK, Neoptolemos JP, Middleton GW (2010) Current status of GV1001 and other telomerase vaccination strategies in the treatment of cancer. Expert Rev Vaccines 9:1007–1016
29. Beatty GL, Vonderheide RH (2008) Telomerase as a universal tumor antigen for cancer vaccines. Expert Rev Vaccines 7:881–887
30. Conforti A, Cipriani B, Peruzzi D, Dharmapuri S, Kandimalla ER, Agrawal S, Mori F, Ciliberto G, La MN, Aurisicchio L (2010) A TLR9 agonist enhances therapeutic effects of telomerase genetic vaccine. Vaccine 28:3522–3530
31. Dharmapuri S, Peruzzi D, Mennuni C, Calvaruso F, Giampaoli S, Barbato G, Kandimalla ER, Agrawal S, Scarselli E, Mesiti G, Ciliberto G, La MN, Aurisicchio L (2009) Coadministration of telomerase genetic vaccine and a novel TLR9 agonist in nonhuman primates. Mol Ther 17:1804–1813
32. Mennuni C, Ugel S, Mori F, Cipriani B, Iezzi M, Pannellini T, Lazzaro D, Ciliberto G, La MN, Zanovello P, Bronte V, Scarselli E (2008) Preventive vaccination with telomerase controls tumor growth in genetically engineered and carcinogen-induced mouse models of cancer. Cancer Res 68:9865–9874
33. Peruzzi D, Gavazza A, Mesiti G, Lubas G, Scarselli E, Conforti A, Bendtsen C, Ciliberto G, La MN, Aurisicchio L (2010) A vaccine targeting telomerase enhances survival of dogs affected by B-cell lymphoma. Mol Ther 18:1559–1567
34. Wenandy L, Sorensen RB, Sengelov L, Svane IM, thor Straten P, Andersen MH (2008) The immunogenicity of the hTERT540-548 peptide in cancer. Clin Cancer Res 14:4–7
35. Liao ZL, Tang XD, Lu MH, Wu YY, Cao YL, Fang DC, Yang SM, Guo H (2012) Antitumor effect of new multiple antigen peptide based on HLA-A0201-restricted CTL epitopes of human telomerase reverse transcriptase (hTERT). Cancer Sci 103:1920–1928
36. Su Z, Dannull J, Yang BK, Dahm P, Coleman D, Yancey D, Sichi S, Niedzwiecki D, Boczkowski D, Gilboa E, Vieweg J (2005) Telomerase mRNA-transfected dendritic cells stimulate antigen-specific CD8+ and CD4+ T cell responses in patients with metastatic prostate cancer. J Immunol 174:3798–3807
37. Rusakiewicz S, Dosset M, Mollier K, Souque P, Charneau P, Wain-Hobson S, Langlade-Demoyen P, Adotevi O (2010) Immunogenicity of a recombinant lentiviral vector carrying human telomerase tumor antigen in HLA-B*0702 transgenic mice. Vaccine 28:6374–6381
38. Adotevi O, Mollier K, Neuveut C, Dosset M, Ravel P, Fridman WH, Tartour E, Charneau P, Wain-Hobson S, Langlade-Demoyen P (2010) Targeting human telomerase reverse transcriptase with recombinant lentivector is highly effective to stimulate antitumor CD8 T-cell immunity in vivo. Blood 115:3025–3032
39. Xue J, Zhu H, Chen Z (2014) Therapeutic vaccines against hepatitis C virus. Infect Genet Evol 22:120–129
40. Wedemeyer H, He XS, Nascimbeni M, Davis AR, Greenberg HB, Hoofnagle JH, Liang TJ, Alter H, Rehermann B (2002) Impaired effector function of hepatitis C virus-specific CD8+ T cells in chronic hepatitis C virus infection. J Immunol 169:3447–3458
41. Lauer GM, Barnes E, Lucas M, Timm J, Ouchi K, Kim AY, Day CL, Robbins GK, Casson DR, Reiser M, Dusheiko G, Allen TM, Chung RT, Walker BD, Klenerman P (2004) High resolution analysis of cellular immune responses in resolved and persistent hepatitis C virus infection. Gastroenterology 127:924–936
42. Guglietta S, Garbuglia AR, Salichos L, Ruggeri L, Folgori A, Perrone MP, Camperio C, Mellace V, Maio G, Maio P, Capobianchi MR, Spada E, Gargano N, Scotta C, Piccolella E, Del PP (2009) Impact of viral selected mutations on T cell mediated immunity in chronically evolving and self limiting acute HCV infection. Virology 386:398–406
43. Urbani S, Uggeri J, Matsuura Y, Miyamura T, Penna A, Boni C, Ferrari C (2001) Identification of immunodominant hepatitis C virus (HCV)-specific cytotoxic T-cell epitopes by stimulation with endogenously synthesized HCV antigens. Hepatology 33:1533–1543
44. Cucchiarini M, Kammer AR, Grabscheid B, Diepolder HM, Gerlach TJ, Gruner N, Santantonio T, Reichen J, Pape GR, Cerny A (2000) Vigorous peripheral blood cytotoxic T cell response during the acute phase of hepatitis C virus infection. Cell Immunol 203:111–123
45. Liyanage UK, Moore TT, Joo HG, Tanaka Y, Herrmann V, Doherty G, Drebin JA, Strasberg SM, Eberlein TJ, Goedegebuure PS, Linehan DC (2002) Prevalence of regulatory T cells is increased in peripheral blood and tumor microenvironment of patients with pancreas or breast adenocarcinoma. J Immunol 169:2756–2761
46. Zou W (2006) Regulatory T cells, tumour immunity and immunotherapy. Nat Rev Immunol 6:295–307
47. Josefowicz SZ, Lu LF, Rudensky AY (2012) Regulatory T cells: mechanisms of differentiation and function. Annu Rev Immunol 30:531–564
48. Peng S, Lyford-Pike S, Akpeng B, Wu A, Hung CF, Hannaman D, Saunders JR, Wu TC, Pai SI (2013) Low-dose cyclophosphamide administered as daily or single dose enhances the antitumor effects of a therapeutic HPV vaccine. Cancer Immunol Immunother 62:171–182
49. Ghiringhelli F, Menard C, Puig PE, Ladoire S, Roux S, Martin F, Solary E, Le CA, Zitvogel L, Chauffert B (2007) Metronomic cyclophosphamide regimen selectively depletes CD4+CD25+ regulatory T cells and restores T and NK effector functions in end stage cancer patients. Cancer Immunol Immunother 56:641–648
50. Ghiringhelli F, Larmonier N, Schmitt E, Parcellier A, Cathelin D, Garrido C, Chauffert B, Solary E, Bonnotte B, Martin F (2004) CD4+CD25+ regulatory T cells suppress tumor immunity but are sensitive to cyclophosphamide which allows immunotherapy of established tumors to be curative. Eur J Immunol 34:336–344
51. Wada S, Yoshimura K, Hipkiss EL, Harris TJ, Yen HR, Goldberg MV, Grosso JF, Getnet D, Demarzo AM, Netto GJ, Anders R, Pardoll DM, Drake CG (2009) Cyclophosphamide augments antitumor immunity: studies in an autochthonous prostate cancer model. Cancer Res 69:4309–4318
52. Lutsiak ME, Semnani RT, De PR, Kashmiri SV, Schlom J, Sabzevari H (2005) Inhibition of CD4(+)25+ T regulatory cell function implicated in enhanced immune response by low-dose cyclophosphamide. Blood 105:2862–2868
53. Emens LA, Armstrong D, Biedrzycki B, Davidson N, Davis-Sproul J, Fetting J, Jaffee E, Onners B, Piantadosi S, Reilly RT, Stearns V, Tartakovsky I, Visvanathan K, Wolff A (2004) A phase I vaccine safety and chemotherapy dose-finding trial of an allogeneic GM-CSF-secreting breast cancer vaccine given in a specifically timed sequence with immunomodulatory doses of cyclophosphamide and doxorubicin. Hum Gene Ther 15:313–337
54. Emens LA, Reilly RT, Jaffee EM (2004) Augmenting the potency of breast cancer vaccines: combined modality immunotherapy. Breast Dis 20:13–24
55. Bass KK, Mastrangelo MJ (1998) Immunopotentiation with low-dose cyclophosphamide in the active specific immunotherapy of cancer. Cancer Immunol Immunother 47:1–12
56. Reagan-Shaw S, Nihal M, Ahmad N (2008) Dose translation from animal to human studies revisited. FASEB J 22:659–661
57. Pinchuk LM, Filipov NM (2008) Differential effects of age on circulating and splenic leukocyte populations in C57BL/6 and BALB/c male mice. Immun Ageing 5:1
58. Serrano-Villar S, Perez-Elias MJ, Dronda F, Casado JL, Moreno A, Royuela A, Perez-Molina JA, Sainz T, Navas E, Hermida JM, Quereda C, Moreno S (2014) Increased risk of serious non-AIDS-related events in HIV-infected subjects on antiretroviral therapy associated with a low CD4/CD8 ratio. PLoS One 9:e85798
59. Chen CA, Ho CM, Chang MC, Sun WZ, Chen YL, Chiang YC, Syu MH, Hsieh CY, Cheng WF (2010) Metronomic chemotherapy enhances antitumor effects of cancer vaccine by depleting regulatory T lymphocytes and inhibiting tumor angiogenesis. Mol Ther 18:1233–1243
60. Garnett CT, Schlom J, Hodge JW (2008) Combination of docetaxel and recombinant vaccine enhances T-cell responses and antitumor activity: effects of docetaxel on immune enhancement. Clin Cancer Res 14:3536–3544
61. Machiels JP, Reilly RT, Emens LA, Ercolini AM, Lei RY, Weintraub D, Okoye FI, Jaffee EM (2001) Cyclophosphamide, doxorubicin, and paclitaxel enhance the antitumor immune response of granulocyte/macrophage-colony stimulating factor-secreting whole-cell vaccines in HER-2/neu tolerized mice. Cancer Res 61:3689–3697
62. Hueman MT, Stojadinovic A, Storrer CE, Foley RJ, Gurney JM, Shriver CD, Ponniah S, Peoples GE (2006) Levels of circulating regulatory CD4+CD25+ T cells are decreased in breast cancer patients after vaccination with a HER2/neu peptide (E75) and GM-CSF vaccine. Breast Cancer Res Treat 98:17–29
63. Gates JD, Clifton GT, Benavides LC, Sears AK, Carmichael MG, Hueman MT, Holmes JP, Jama YH, Mursal M, Zacharia A, Ciano K, Khoo S, Stojadinovic A, Ponniah S, Peoples GE (2010) Circulating regulatory T cells (CD4+CD25+FOXP3+) decrease in breast cancer patients after vaccination with a modified MHC class II HER2/neu (AE37) peptide. Vaccine 28:7476–7482
64. Nakai N, Katoh N, Kitagawa T, Ueda E, Takenaka H, Kishimoto S (2009) Immunoregulatory T cells in the peripheral blood of melanoma patients treated with melanoma antigen-pulsed mature monocyte-derived dendritic cell vaccination. J Dermatol Sci 54:31–37
65. Cipriani B, Fridman A, Bendtsen C, Dharmapuri S, Mennuni C, Pak I, Mesiti G, Forni G, Monaci P, Bagchi A, Ciliberto G, La MN, Scarselli E (2008) Therapeutic vaccination halts disease progression in BALB-neuT mice: the amplitude of elicited immune response is predictive of vaccine efficacy. Hum Gene Ther 19:670–680
66. Papewalis C, Wuttke M, Jacobs B, Domberg J, Willenberg H, Baehring T, Cupisti K, Raffel A, Chao L, Fenk R, Seissler J, Scherbaum WA, Schott M (2008) Dendritic cell vaccination induces tumor epitope-specific Th1 immune response in medullary thyroid carcinoma. Horm Metab Res 40:108–116
67. Hus I, Schmitt M, Tabarkiewicz J, Radej S, Wojas K, Bojarska-Junak A, Schmitt A, Giannopoulos K, Dmoszynska A, Rolinski J (2008) Vaccination of B-CLL patients with autologous dendritic cells can change the frequency of leukemia antigen-specific CD8+ T cells as well as CD4+CD25+FoxP3+ regulatory T cells toward an antileukemia response. Leukemia 22:1007–1017
68. Hao S, Liu Y, Yuan J, Zhang X, He T, Wu X, Wei Y, Sun D, Xiang J (2007) Novel exosome-targeted CD4+ T cell vaccine counteracting CD4+25+ regulatory T cell-mediated immune suppression and stimulating efficient central memory CD8+ CTL responses. J Immunol 179:2731–2740
69. Ikezawa Y, Nakazawa M, Tamura C, Takahashi K, Minami M, Ikezawa Z (2005) Cyclophosphamide decreases the number, percentage and the function of CD25+CD4+ regulatory T cells, which suppress induction of contact hypersensitivity. J Dermatol Sci 39:105–112