Pharmacological modulation of anti-tumor immunity induced by oncolytic viruses

Frontiers in Oncology

Volumn 4, Issue JUL, 2014, Pages

  Forbes, Nicole E ^a,b   Krishnan, Ramya ^a,b   Diallo, Jean Simon ^a,b  

^a OTTAWA HOSPITAL RESEARCH INSTITUTE   (Canada)

^b UNIVERSITY OF OTTAWA   (Canada)

Author keywords

Anti tumor immunity; Cancer; Chemotherapy; Combination therapy; Immuno modulatory therapy; Oncolytic virotherapy; Pharmacological therapy

Indexed keywords

BORTEZOMIB; CYCLOPHOSPHAMIDE; DECITABINE; ENTINOSTAT; GAMMA INTERFERON; GEMCITABINE; HISTONE DEACETYLASE INHIBITOR; I KAPPA B; I KAPPA B BETA; INTERLEUKIN 2; IRINOTECAN; MITOXANTRONE; ONCOLYTIC VIRUS; PHOSPHATIDYLINOSITOL 3 KINASE; PLATELET DERIVED GROWTH FACTOR RECEPTOR; RIBONUCLEOTIDE REDUCTASE; SUNITINIB; TEMOZOLOMIDE; TRICHOSTATIN A; TRIPTOLIDE; TUMOR NECROSIS FACTOR; VALPROIC ACID; VASCULOTROPIN RECEPTOR; VORINOSTAT;

ADENOVIRIDAE; APOPTOSIS; DENDRITIC CELL; GASTROINTESTINAL STROMAL TUMOR; HEMATOPOIETIC STEM CELL; HERPES SIMPLEX VIRUS 1; IMMUNE RESPONSE; IMMUNOMODULATION; IMMUNOSUPPRESSIVE TREATMENT; LIVER CELL CARCINOMA; LYMPHOCYTE; MACROPHAGE; MEASLES; MONOCYTE; MYELOID PROGENITOR CELL; MYXOMA VIRUS; NATURAL KILLER CELL; NONHUMAN; PARVOVIRIDAE; REOVIRIDAE; REVIEW; SENSITIZATION; TUMOR IMMUNITY; VACCINIA; VESICULOVIRUS;

EID: 84987984981     PISSN: None     EISSN: 2234943X     Source Type: Journal    
DOI: 10.3389/fonc.2014.00191     Document Type: Review

References (138)

1. Forbes NE, Abdelbary H, Lupien M, Bell JC, Diallo JS. Exploiting tumor epigenetics to improve oncolytic virotherapy. Front Genet (2013) 4:184. doi: 10.3389/fgene.2013.00184
2. Ilkow CS, Swift SL, Bell JC, Diallo JS. From scourge to cure: tumour-selective viral pathogenesis as a new strategy against cancer. PLoS Pathog (2014) 10:e1003836. doi:10.1371/journal.ppat.1003836
3. Prestwich RJ, Errington F, Ilett EJ, Morgan RS, Scott KJ, Kottke T, et al. Tumor infection by oncolytic reovirus primes adaptive antitumor immunity. Clin Cancer Res (2008) 14:7358-66. doi:10.1158/1078-0432.CCR-08-0831
4. Gujar SA, Pan DA, Marcato P, Garant KA, Lee PW. Oncolytic virus-initiated protective immunity against prostate cancer. Mol Ther (2011) 19:797-804. doi:10.1038/mt.2010.297
5. Steele L, Errington F, Prestwich R, Ilett E, Harrington K, Pandha H, et al. Pro-inflammatory cytokine/chemokine production by reovirus treated melanoma cells is PKR/NF-kappaB mediated and supports innate and adaptive anti-tumour immune priming. Mol Cancer (2011) 10:20. doi:10.1186/1476-4598-10-20
6. Russell SJ, Peng KW, Bell JC. Oncolytic virotherapy. Nat Biotechnol (2012) 30:658-70. doi:10.1038/nbt.2287
7. Park BH, Hwang T, Liu TC, Sze DY, Kim JS, Kwon HC, et al. Use of a targeted oncolytic poxvirus, JX-594, in patients with refractory primary or metastatic liver cancer: a phase I trial. Lancet Oncol (2008) 9:533-42. doi:10.1016/S1470-2045(08)70107-4
8. Galanis E, Markovic SN, Suman VJ, Nuovo GJ, Vile RG, Kottke TJ, et al. Phase II trial of intravenous administration of Reolysin((R)) (Reovirus Serotype-3-dearing Strain) in patients with metastatic melanoma. Mol Ther (2012) 20:1998-2003. doi:10.1038/mt.2012.146
9. Kim KH, Dmitriev IP, Saddekni S, Kashentseva EA, Harris RD, Aurigemma R, et al. A phase I clinical trial of Ad5/3-Delta24, a novel serotype-chimeric, infectivity-enhanced, conditionally-replicative adenovirus (CRAd), in patients with recurrent ovarian cancer. Gynecol Oncol (2013) 130:518-24. doi:10.1016/j.ygyno.2013.06.003
10. Morris DG, Feng X, Difrancesco LM, Fonseca K, Forsyth PA, Paterson AH, et al. REO-001: a phase I trial of percutaneous intralesional administration of reovirus type 3 dearing (Reolysin(R)) in patients with advanced solid tumors. Invest New Drugs (2013) 31:696-706. doi:10.1007/s10637-012-9865-z
11. Garber K. China approves world's first oncolytic virus therapy for cancer treatment. J Natl Cancer Inst (2006) 98:298-300. doi:10.1093/jnci/djj111
12. Andtbacka RH, Collichio FA, Amatruda T, Senzer NN, Chesney J, Delman KA, et al. OPTiM: a randomized phase III trial of talimogene laherparepvec (T-VEC) versus subcutaneous (SC) granulocyte-macrophage colony-stimulating factor (GM-CSF) for the treatment (tx) of unresected stage IIIB/C and IV melanoma. J Clin Oncol (2013) 31:LBA9008.
13. Helfand C. Amgen to Pursue T-Vec Approval Despite PhIII Survival Miss [Online]. FierceMarkets. (2014) [cited 2014 Jun 24]. Available from: http://www.fiercevaccines.com/story/amgen-pursue-t-vec-approval-despite-phiii-survival-miss/2014-06-03? utm_medium=nl&utm_source=internal
14. Senzer NN, Kaufman HL, Amatruda T, Nemunaitis M, Reid T, Daniels G, et al. Phase II clinical trial of a granulocyte-macrophage colony-stimulating factor-encoding, second-generation oncolytic herpesvirus in patients with unresectable metastatic melanoma. J Clin Oncol (2009) 27:5763-71. doi:10.1200/JCO.2009.24.3675
15. Breitbach CJ, Burke J, Jonker D, Stephenson J, Haas AR, Chow LQ, et al. Intravenous delivery of a multi-mechanistic cancer-targeted oncolytic poxvirus in humans. Nature (2011) 477:99-102. doi:10.1038/nature10358
16. Heo J, Reid T, Ruo L, Breitbach CJ, Rose S, Bloomston M, et al. Randomized dose-finding clinical trial of oncolytic immunotherapeutic vaccinia JX-594 in liver cancer. Nat Med (2013) 19:329-36. doi:10.1038/nm.3089
17. Ottolino-Perry K, Diallo JS, Lichty BD, Bell JC, Andrea Mccart J. Intelligent design: combination therapy with oncolytic viruses. Mol Ther (2010) 18:251-63. doi:10.1038/mt.2009.283
18. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell (2011) 144:646-74. doi:10.1016/j.cell.2011.02.013
19. Emadi A, Jones RJ, Brodsky RA. Cyclophosphamide and cancer: golden anniversary. Nat Rev Clin Oncol (2009) 6:638-47. doi:10.1038/nrclinonc.2009.146
20. Ikeda K, Ichikawa T, Wakimoto H, Silver JS, Deisboeck TS, Finkelstein D, et al. Oncolytic virus therapy of multiple tumors in the brain requires suppression of innate and elicited antiviral responses. Nat Med (1999) 5:881-7. doi:10.1038/11320
21. Ikeda K, Wakimoto H, Ichikawa T, Jhung S, Hochberg FH, Louis DN, et al. Complement depletion facilitates the infection of multiple brain tumors by an intravascular, replication-conditional herpes simplex virus mutant. J Virol (2000) 74:4765-75. doi:10.1128/JVI.74.10.4765-4775.2000
22. Wakimoto H, Fulci G, Tyminski E, Chiocca EA. Altered expression of antiviral cytokine mRNAs associated with cyclophosphamide's enhancement of viral oncolysis. Gene Ther (2004) 11:214-23. doi:10.1038/sj.gt.3302143
23. Fulci G, Breymann L, Gianni D, Kurozomi K, Rhee SS, Yu J, et al. Cyclophosphamide enhances glioma virotherapy by inhibiting innate immune responses. Proc Natl Acad Sci U S A (2006) 103:12873-8. doi:10.1073/pnas.0605496103
24. Currier MA, Gillespie RA, Sawtell NM, Mahller YY, Stroup G, Collins MH, et al. Efficacy and safety of the oncolytic herpes simplex virus rRp450 alone and combined with cyclophosphamide. Mol Ther (2008) 16:879-85. doi:10.1038/mt.2008.49
25. Thomas MA, Spencer JF, Toth K, Sagartz JE, Phillips NJ, Wold WS. Immunosuppression enhances oncolytic adenovirus replication and antitumor efficacy in the Syrian hamster model. Mol Ther (2008) 16:1665-73. doi:10.1038/mt.2008.162
26. Dhar D, Spencer JF, Toth K, Wold WS. Effect of preexisting immunity on oncolytic adenovirus vector INGN 007 antitumor efficacy in immunocompetent and immunosuppressed Syrian hamsters. J Virol (2009) 83:2130-9. doi:10.1128/JVI.02127-08
27. Cerullo V, Diaconu I, Kangasniemi L, Rajecki M, Escutenaire S, Koski A, et al. Immunological effects of low-dose cyclophosphamide in cancer patients treated with oncolytic adenovirus. Mol Ther (2011) 19:1737-46. doi:10.1038/mt.2011.113
28. Hasegawa N, Abei M, Yokoyama KK, Fukuda K, Seo E, Kawashima R, et al. Cyclophosphamide enhances antitumor efficacy of oncolytic adenovirus expressing uracil phosphoribosyltransferase (UPRT) in immunocompetent Syrian hamsters. Int J Cancer (2013) 133:1479-88. doi:10.1002/ijc.28132
29. Lun XQ, Jang JH, Tang N, Deng H, Head R, Bell JC, et al. Efficacy of systemically administered oncolytic vaccinia virotherapy for malignant gliomas is enhanced by combination therapy with rapamycin or cyclophosphamide. Clin Cancer Res (2009) 15:2777-88. doi:10.1158/1078-0432.CCR-08-2342
30. Qiao J, Wang H, Kottke T, White C, Twigger K, Diaz RM, et al. Cyclophosphamide facilitates antitumor efficacy against subcutaneous tumors following intravenous delivery of reovirus. Clin Cancer Res (2008) 14:259-69. doi:10.1158/1078-0432.CCR-07-1510
31. Ungerechts G, Springfeld C, Frenzke ME, Lampe J, Parker WB, Sorscher EJ, et al. An immunocompetent murine model for oncolysis with an armed and targeted measles virus. Mol Ther (2007) 15:1991-7. doi:10.1038/sj.mt.6300291
32. Ungerechts G, Frenzke ME, Yaiw KC, Miest T, Johnston PB, Cattaneo R. Mantle cell lymphoma salvage regimen: synergy between a reprogrammed oncolytic virus and two chemotherapeutics. Gene Ther (2010) 17:1506-16. doi:10.1038/gt.2010.103
33. Peng KW, Myers R, Greenslade A, Mader E, Greiner S, Federspiel MJ, et al. Using clinically approved cyclophosphamide regimens to control the humoral immune response to oncolytic viruses. Gene Ther (2013) 20:255-61. doi:10.1038/gt.2012.31
34. Kottke T, Thompson J, Diaz RM, Pulido J, Willmon C, Coffey M, et al. Improved systemic delivery of oncolytic reovirus to established tumors using preconditioning with cyclophosphamide-mediated Treg modulation and interleukin-2. Clin Cancer Res (2009) 15:561-9. doi:10.1158/1078-0432.CCR-08-1688
35. Mini E, Nobili S, Caciagli B, Landini I, Mazzei T. Cellular pharmacology of gemcitabine. Ann Oncol (2006) 17(Suppl 5):v7-12. doi:10.1093/annonc/mdj941
36. Lolkema MP, Arkenau HT, Harrington K, Roxburgh P, Morrison R, Roulstone V, et al. A phase I study of the combination of intravenous reovirus type 3 Dearing and gemcitabine in patients with advanced cancer. Clin Cancer Res (2011) 17:581-8. doi:10.1158/1078-0432.CCR-10-2159
37. Gabrilovich DI, Nagaraj S. Myeloid-derived suppressor cells as regulators of the immune system. Nat Rev Immunol (2009) 9:162-74. doi:10.1038/nri2506
38. Leitner S, Sweeney K, Oberg D, Davies D, Miranda E, Lemoine NR, et al. Oncolytic adenoviral mutants with E1B19K gene deletions enhance gemcitabine-induced apoptosis in pancreatic carcinoma cells and anti-tumor efficacy in vivo. Clin Cancer Res (2009) 15:1730-40. doi:10.1158/1078-0432.CCR-08-2008
39. Liu D, Kojima T, Ouchi M, Kuroda S, Watanabe Y, Hashimoto Y, et al. Preclinical evaluation of synergistic effect of telomerase-specific oncolytic virotherapy and gemcitabine for human lung cancer. Mol Cancer Ther (2009) 8:980-7. doi:10.1158/1535-7163.MCT-08-0901
40. Onimaru M, Ohuchida K, Nagai E, Mizumoto K, Egami T, Cui L, et al. Combination with low-dose gemcitabine and hTERT-promoter-dependent conditionally replicative adenovirus enhances cytotoxicity through their crosstalk mechanisms in pancreatic cancer. Cancer Lett (2010) 294:178-86. doi:10.1016/j.canlet.2010.01.034
41. Bhattacharyya M, Francis J, Eddouadi A, Lemoine NR, Hallden G. An oncolytic adenovirus defective in pRb-binding (dl922-947) can efficiently eliminate pancreatic cancer cells and tumors in vivo in combination with 5-FU or gemcitabine. Cancer Gene Ther (2011) 18:734-43. doi:10.1038/cgt.2011.45
42. Cherubini G, Kallin C, Mozetic A, Hammaren-Busch K, Muller H, Lemoine NR, et al. The oncolytic adenovirus Addd enhances selective cancer cell killing in combination with DNA-damaging drugs in pancreatic cancer models. Gene Ther (2011) 18:1157-65. doi:10.1038/gt.2011.141
43. Wang H, Satoh M, Chen GP, Li DC, Hamada H, Arai Y. E1A, E1B double-restricted adenovirus enhances the cytotoxicity and antitumor activity of gemcitabine to renal cell carcinoma. Chin Med J (Engl) (2011) 124:1082-7.
44. Kangasniemi L, Parviainen S, Pisto T, Koskinen M, Jokinen M, Kiviluoto T, et al. Effects of capsid-modified oncolytic adenoviruses and their combinations with gemcitabine or silica gel on pancreatic cancer. Int J Cancer (2012) 131:253-63. doi:10.1002/ijc.26370
45. Angelova AL, Aprahamian M, Grekova SP, Hajri A, Leuchs B, Giese NA, et al. Improvement of gemcitabine-based therapy of pancreatic carcinoma by means of oncolytic parvovirus H-1PV. Clin Cancer Res (2009) 15:511-9. doi:10.1158/1078-0432.CCR-08-1088
46. Angelova AL, Grekova SP, Heller A, Kuhlmann O, Soyka E, Giese T, et al. Complementary induction of immunogenic cell death by oncolytic parvovirus H-1PV and gemcitabine in pancreatic cancer. J Virol (2014) 88:5263-76. doi:10.1128/JVI.03688-13
47. Sei S, Mussio JK, Yang QE, Nagashima K, Parchment RE, Coffey MC, et al. Synergistic antitumor activity of oncolytic reovirus and chemotherapeutic agents in non-small cell lung cancer cells. Mol Cancer (2009) 8:47. doi:10.1186/1476-4598-8-47
48. Gujar SA, Clements D, Dielschneider R, Helson E, Marcato P, Lee PW. Gemcitabine enhances the efficacy of reovirus-based oncotherapy through anti-tumour immunological mechanisms. Br J Cancer (2014) 110:83-93. doi:10.1038/bjc.2013.695
49. Hastie E, Besmer DM, Shah NR, Murphy AM, Moerdyk-Schauwecker M, Molestina C, et al. Oncolytic vesicular stomatitis virus in an immunocompetent model of MUC1-positive or MUC1-null pancreatic ductal adenocarcinoma. J Virol (2013) 87:10283-94. doi:10.1128/JVI.01412-13
50. Watanabe I, Kasuya H, Nomura N, Shikano T, Shirota T, Kanazumi N, et al. Effects of tumor selective replication-competent herpes viruses in combination with gemcitabine on pancreatic cancer. Cancer Chemother Pharmacol (2008) 61:875-82. doi:10.1007/s00280-007-0567-8
51. Esaki S, Goshima F, Kimura H, Murakami S, Nishiyama Y. Enhanced antitumoral activity of oncolytic herpes simplex virus with gemcitabine using colorectal tumor models. Int J Cancer (2013) 132:1592-601. doi:10.1002/ijc.27823
52. Yu YA, Galanis C, Woo Y, Chen N, Zhang Q, Fong Y, et al. Regression of human pancreatic tumor xenografts in mice after a single systemic injection of recombinant vaccinia virus GLV-1h68. Mol Cancer Ther (2009) 8:141-51. doi:10.1158/1535-7163.MCT-08-0533
53. Wennier ST, Liu J, Li S, Rahman MM, Mona M, Mcfadden G. Myxoma virus sensitizes cancer cells to gemcitabine and is an effective oncolytic virotherapeutic in models of disseminated pancreatic cancer. Mol Ther (2012) 20:759-68. doi:10.1038/mt.2011.293
54. Bonvini P, Zorzi E, Basso G, Rosolen A. Bortezomib-mediated 26S proteasome inhibition causes cell-cycle arrest and induces apoptosis in CD-30+ anaplastic large cell lymphoma. Leukemia (2007) 21:838-42. doi:10.1038/sj.leu.2404528
55. Berenson JR, Ma HM, Vescio R. The role of nuclear factor-kappaB in the biology and treatment of multiple myeloma. Semin Oncol (2001) 28:626-33. doi:10.1053/sonc.2001.29542
56. Diallo JS, Betton B, Parent N, Peant B, Lessard L, Le Page C, et al. Enhanced killing of androgen-independent prostate cancer cells using inositol hexakisphosphate in combination with proteasome inhibitors. Br J Cancer (2008) 99:1613-22. doi:10.1038/sj.bjc.6604730
57. Nawrocki ST, Carew JS, Dunner K Jr., Boise LH, Chiao PJ, Huang P, et al. Bortezomib inhibits PKR-like endoplasmic reticulum (ER) kinase and induces apoptosis via ER stress in human pancreatic cancer cells. Cancer Res (2005) 65:11510-9. doi:10.1158/0008-5472.CAN-05-2370
58. Marshansky V, Wang X, Bertrand R, Luo H, Duguid W, Chinnadurai G, et al. Proteasomes modulate balance among proapoptotic and antiapoptotic Bcl-2 family members and compromise functioning of the electron transport chain in leukemic cells. J Immunol (2001) 166:3130-42. doi:10.4049/jimmunol.166.5.3130
59. Chang CL, Hsu YT, Wu CC, Yang YC, Wang C, Wu TC, et al. Immune mechanism of the antitumor effects generated by bortezomib. J Immunol (2012) 189:3209-20. doi:10.4049/jimmunol.1103826
60. Berges C, Haberstock H, Fuchs D, Miltz M, Sadeghi M, Opelz G, et al. Proteasome inhibition suppresses essential immune functions of human CD4+ T cells. Immunology (2008) 124:234-46. doi:10.1111/j.1365-2567.2007.02761.x
61. Yarde DN, Nace RA, Russell SJ. Oncolytic vesicular stomatitis virus and bortezomib are antagonistic against myeloma cells in vitro but have additive anti-myeloma activity in vivo. Exp Hematol (2013) 41:1038-49. doi:10.1016/j.exphem.2013.09.005
62. Carew JS, Espitia CM, Zhao W, Kelly KR, Coffey M, Freeman JW, et al. Reolysin is a novel reovirus-based agent that induces endoplasmic reticular stress-mediated apoptosis in pancreatic cancer. Cell Death Dis (2013) 4:e728. doi:10.1038/cddis.2013.259
63. Boozari B, Mundt B, Woller N, Struver N, Gurlevik E, Schache P, et al. Antitumoural immunity by virus-mediated immunogenic apoptosis inhibits metastatic growth of hepatocellular carcinoma. Gut (2010) 59:1416-26. doi:10.1136/gut.2009.196519
64. Mazerski J, Martelli S, Borowski E. The geometry of intercalation complex of antitumor mitoxantrone and ametantrone with DNA: molecular dynamics simulations. Acta Biochim Pol (1998) 45:1-11.
65. Fidler JM, Dejoy SQ, Smith FR III, Gibbons JJ Jr. Selective immunomodulation by the antineoplastic agent mitoxantrone. II. Nonspecific adherent suppressor cells derived from mitoxantrone-treated mice. J Immunol (1986) 136:2747-54.
66. Neuhaus O, Wiendl H, Kieseier BC, Archelos JJ, Hemmer B, Stuve O, et al. Multiple sclerosis: mitoxantrone promotes differential effects on immunocompetent cells in vitro. J Neuroimmunol (2005) 168:128-37. doi:10.1016/j.jneuroim.2005.01.024
67. Kopadze T, Dehmel T, Hartung HP, Stuve O, Kieseier BC. Inhibition by mitoxantrone of in vitro migration of immunocompetent cells: a possible mechanism for therapeutic efficacy in the treatment of multiple sclerosis. Arch Neurol (2006) 63:1572-8. doi:10.1001/archneur.63.11.1572
68. Okuda DT. Immunosuppressive treatments in multiple sclerosis. Handb Clin Neurol (2014) 122:503-11. doi:10.1016/B978-0-444-52001-2.00022-4
69. Workenhe S, Pol JG, Lichty BD, Cummings DT, Mossman KL. Combining oncolytic HSV-1 with immunogenic cell death-inducing drug mitoxantrone breaks cancer immune tolerance and improves therapeutic efficacy. Cancer Immunol Res (2013) 1:1-11. doi:10.1158/2326-6066.CIR-13-0059-T
70. Oberg D, Yanover E, Adam V, Sweeney K, Costas C, Lemoine NR, et al. Improved potency and selectivity of an oncolytic E1ACR2 and E1B19K deleted adenoviral mutant in prostate and pancreatic cancers. Clin Cancer Res (2010) 16:541-53. doi:10.1158/1078-0432.CCR-09-1960
71. Radhakrishnan S, Miranda E, Ekblad M, Holford A, Pizarro MT, Lemoine NR, et al. Efficacy of oncolytic mutants targeting pRb and p53 pathways is synergistically enhanced when combined with cytotoxic drugs in prostate cancer cells and tumor xenografts. Hum Gene Ther (2010) 21:1311-25. doi:10.1089/hum.2010.019
72. Miranda E, Maya Pineda H, Oberg D, Cherubini G, Garate Z, Lemoine NR, et al. Adenovirus-mediated sensitization to the cytotoxic drugs docetaxel and mitoxantrone is dependent on regulatory domains in the E1ACR1 gene-region. PLoS One (2012) 7:e46617. doi:10.1371/journal.pone.0046617
73. Maeda K, Hazama S, Tokuno K, Kan S, Maeda Y, Watanabe Y, et al. Impact of chemotherapy for colorectal cancer on regulatory T-cells and tumor immunity. Anticancer Res (2011) 31:4569-74.
74. Tyminski E, Leroy S, Terada K, Finkelstein DM, Hyatt JL, Danks MK, et al. Brain tumor oncolysis with replication-conditional herpes simplex virus type 1 expressing the prodrug-activating genes, CYP2B1 and secreted human intestinal carboxylesterase, in combination with cyclophosphamide and irinotecan. Cancer Res (2005) 65:6850-7. doi:10.1158/0008-5472.CAN-05-0154
75. Granot T, Meruelo D. The role of natural killer cells in combinatorial anti-cancer therapy using Sindbis viral vectors and irinotecan. Cancer Gene Ther (2012) 19:588-91. doi:10.1038/cgt.2012.33
76. Stupp R, Mason WP, Van Den Bent MJ, Weller M, Fisher B, Taphoorn MJ, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med (2005) 352:987-96. doi:10.1056/NEJMoa043330
77. Middleton MR, Grob JJ, Aaronson N, Fierlbeck G, Tilgen W, Seiter S, et al. Randomized phase III study of temozolomide versus dacarbazine in the treatment of patients with advanced metastatic malignant melanoma. J Clin Oncol (2000) 18:158-66.
78. Sanchez-Perez LA, Choi BD, Archer GE, Cui X, Flores C, Johnson LA, et al. Myeloablative temozolomide enhances CD8(+) T-cell responses to vaccine and is required for efficacy against brain tumors in mice. PLoS One (2013) 8:e59082. doi:10.1371/journal.pone.0059082
79. Banissi C, Ghiringhelli F, Chen L, Carpentier AF. Treg depletion with a low-dose metronomic temozolomide regimen in a rat glioma model. Cancer Immunol Immunother (2009) 58:1627-34. doi:10.1007/s00262-009-0671-1
80. Alonso MM, Gomez-Manzano C, Jiang H, Bekele NB, Piao Y, Yung WK, et al. Combination of the oncolytic adenovirus ICOVIR-5 with chemotherapy provides enhanced anti-glioma effect in vivo. Cancer Gene Ther (2007) 14:756-61. doi:10.1038/sj.cgt.7701067
81. Holzmuller R, Mantwill K, Haczek C, Rognoni E, Anton M, Kasajima A, et al. YB-1 dependent virotherapy in combination with temozolomide as a multimodal therapy approach to eradicate malignant glioma. Int J Cancer (2011) 129:1265-76. doi:10.1002/ijc.25783
82. Liikanen I, Ahtiainen L, Hirvinen ML, Bramante S, Cerullo V, Nokisalmi P, et al. Oncolytic adenovirus with temozolomide induces autophagy and antitumor immune responses in cancer patients. Mol Ther (2013) 21:1212-23. doi:10.1038/mt.2013.51
83. Tobias AL, Thaci B, Auffinger B, Rincon E, Balyasnikova IV, Kim CK, et al. The timing of neural stem cell-based virotherapy is critical for optimal therapeutic efficacy when applied with radiation and chemotherapy for the treatment of glioblastoma. Stem Cells Transl Med (2013) 2:655-66. doi:10.5966/sctm.2013-0039
84. Aghi M, Rabkin S, Martuza RL. Effect of chemotherapy-induced DNA repair on oncolytic herpes simplex viral replication. J Natl Cancer Inst (2006) 98:38-50. doi:10.1093/jnci/djj003
85. Kanai R, Rabkin SD, Yip S, Sgubin D, Zaupa CM, Hirose Y, et al. Oncolytic virus-mediated manipulation of DNA damage responses: synergy with chemotherapy in killing glioblastoma stem cells. J Natl Cancer Inst (2012) 104:42-55. doi:10.1093/jnci/djr509
86. Jha BK, Polyakova I, Kessler P, Dong B, Dickerman B, Sen GC, et al. Inhibition of RNase L and RNA-dependent protein kinase (PKR) by sunitinib impairs antiviral innate immunity. J Biol Chem (2011) 286:26319-26. doi:10.1074/jbc.M111.253443
87. Kottke T, Hall G, Pulido J, Diaz RM, Thompson J, Chong H, et al. Antiangiogenic cancer therapy combined with oncolytic virotherapy leads to regression of established tumors in mice. J Clin Invest (2010) 120:1551-60. doi:10.1172/JCI41431
88. Jha BK, Dong B, Nguyen CT, Polyakova I, Silverman RH. Suppression of antiviral innate immunity by sunitinib enhances oncolytic virotherapy. Mol Ther (2013) 21:1749-57. doi:10.1038/mt.2013.112
89. Hou W, Chen H, Rojas J, Sampath P, Thorne SH. Oncolytic vaccinia virus demonstrates antiangiogenic effects mediated by targeting of VEGF. Int J Cancer (2014) 135:1238-46. doi:10.1002/ijc.28747
90. Breitbach CJ, Paterson JM, Lemay CG, Falls TJ, Mcguire A, Parato KA, et al. Targeted inflammation during oncolytic virus therapy severely compromises tumor blood flow. Mol Ther (2007) 15:1686-93. doi:10.1038/sj.mt.6300215
91. Liu TC, Hwang T, Park BH, Bell J, Kirn DH. The targeted oncolytic poxvirus JX-594 demonstrates antitumoral, antivascular, and anti-HBV activities in patients with hepatocellular carcinoma. Mol Ther (2008) 16:1637-42. doi:10.1038/mt.2008.143
92. Breitbach CJ, Arulanandam R, De Silva N, Thorne SH, Patt R, Daneshmand M, et al. Oncolytic vaccinia virus disrupts tumor-associated vasculature in humans. Cancer Res (2013) 73:1265-75. doi:10.1158/0008-5472.CAN-12-2687
93. Magnani L, Eeckhoute J, Lupien M. Pioneer factors: directing transcriptional regulators within the chromatin environment. Trends Genet (2011) 27:465-74. doi:10.1016/j.tig.2011.07.002
94. Picaud S, Bardot B, De Maeyer E, Seif I. Enhanced tumor development in mice lacking a functional type I interferon receptor. J Interferon Cytokine Res (2002) 22:457-62. doi:10.1089/10799900252952244
95. Dunn GP, Koebel CM, Schreiber RD. Interferons, immunity and cancer immunoediting. Nat Rev Immunol (2006) 6:836-48. doi:10.1038/nri1961
96. Uno K, Hirosaki M, Kakimi K, Tominaga M, Suginoshita Y, Hasegawa G, et al. Impaired IFN-alpha production and the risk of cancer development. J Interferon Cytokine Res (2007) 27:1013-7. doi:10.1089/jir.2007.0047
97. Stojdl DF, Lichty BD, Tenoever BR, Paterson JM, Power AT, Knowles S, et al. VSV strains with defects in their ability to shutdown innate immunity are potent systemic anti-cancer agents. Cancer Cell (2003) 4:263-75. doi:10.1016/S1535-6108(03)00241-1
98. Naka K, Abe K, Takemoto K, Dansako H, Ikeda M, Shimotohno K, et al. Epigenetic silencing of interferon-inducible genes is implicated in interferon resistance of hepatitis C virus replicon-harboring cells. J Hepatol (2006) 44:869-78. doi:10.1016/j.jhep.2006.01.030
99. Nguyen TL, Abdelbary H, Arguello M, Breitbach C, Leveille S, Diallo JS, et al. Chemical targeting of the innate antiviral response by histone deacetylase inhibitors renders refractory cancers sensitive to viral oncolysis. Proc Natl Acad Sci U S A (2008) 105:14981-6. doi:10.1073/pnas.0803988105
100. Fang TC, Schaefer U, Mecklenbrauker I, Stienen A, Dewell S, Chen MS, et al. Histone H3 lysine 9 di-methylation as an epigenetic signature of the interferon response. J Exp Med (2012) 209:661-9. doi:10.1084/jem.20112343
101. Chen Q, Denard B, Huang H, Ye J. Epigenetic silencing of antiviral genes renders clones of Huh-7 cells permissive for hepatitis C virus replication. J Virol (2013) 87:659-65. doi:10.1128/JVI.01984-12
102. Cho H, Proll SC, Szretter KJ, Katze MG, Gale M Jr, Diamond MS. Differential innate immune response programs in neuronal subtypes determine susceptibility to infection in the brain by positive-stranded RNA viruses. Nat Med (2013) 19:458-64. doi:10.1038/nm.3108
103. Chang HM, Paulson M, Holko M, Rice CM, Williams BR, Marie I, et al. Induction of interferon-stimulated gene expression and antiviral responses require protein deacetylase activity. Proc Natl Acad Sci U S A (2004) 101:9578-83. doi:10.1073/pnas.0400567101
104. Katsura T, Iwai S, Ota Y, Shimizu H, Ikuta K, Yura Y. The effects of trichostatin A on the oncolytic ability of herpes simplex virus for oral squamous cell carcinoma cells. Cancer Gene Ther (2009) 16:237-45. doi:10.1038/cgt.2008.81
105. Liu TC, Castelo-Branco P, Rabkin SD, Martuza RL. Trichostatin A and oncolytic HSV combination therapy shows enhanced antitumoral and antiangiogenic effects. Mol Ther (2008) 16:1041-7. doi:10.1038/mt.2008.58
106. Otsuki A, Patel A, Kasai K, Suzuki M, Kurozumi K, Chiocca EA, et al. Histone deacetylase inhibitors augment antitumor efficacy of herpes-based oncolytic viruses. Mol Ther (2008) 16:1546-55. doi:10.1038/mt.2008.155
107. Alvarez-Breckenridge CA, Yu J, Price R, Wei M, Wang Y, Nowicki MO, et al. The histone deacetylase inhibitor valproic acid lessens NK cell action against oncolytic virus-infected glioblastoma cells by inhibition of STAT5/T-BET signaling and generation of gamma interferon. J Virol (2012) 86:4566-77. doi:10.1128/JVI.05545-11
108. MacTavish H, Diallo JS, Huang B, Stanford M, Le Boeuf F, De Silva N, et al. Enhancement of vaccinia virus based oncolysis with histone deacetylase inhibitors. PLoS One (2010) 5:e14462. doi:10.1371/journal.pone.0014462
109. Bridle BW, Chen L, Lemay CG, Diallo JS, Pol J, Nguyen A, et al. HDAC inhibition suppresses primary immune responses, enhances secondary immune responses, and abrogates autoimmunity during tumor immunotherapy. Mol Ther (2013) 21:887-94. doi:10.1038/mt.2012.265
110. Cedar H, Bergman Y. Linking DNA methylation and histone modification: patterns and paradigms. Nat Rev Genet (2009) 10:295-304. doi:10.1038/nrg2540
111. Okemoto K, Kasai K, Wagner B, Haseley A, Meisen H, Bolyard C, et al. DNA demethylating agents synergize with oncolytic HSV1 against malignant gliomas. Clin Cancer Res (2013) 19:5952-9. doi:10.1158/1078-0432.CCR-12-3588
112. Wong KK, Engelman JA, Cantley LC. Targeting the PI3K signaling pathway in cancer. Curr Opin Genet Dev (2010) 20:87-90. doi:10.1016/j.gde.2009.11.002
113. Uddin S, Fish EN, Sher DA, Gardziola C, White MF, Platanias LC. Activation of the phosphatidylinositol 3-kinase serine kinase by IFN-alpha. J Immunol (1997) 158:2390-7.
114. Martini M, Ciraolo E, Gulluni F, Hirsch E. Targeting PI3K in cancer: any good news? Front Oncol (2013) 3:108. doi:10.3389/fonc.2013.00108
115. Vlahos CJ, Matter WF, Hui KY, Brown RF. A specific inhibitor of phosphatidylinositol 3-kinase, 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one (LY294002). J Biol Chem (1994) 269:5241-8.
116. Kanai R, Wakimoto H, Martuza RL, Rabkin SD. A novel oncolytic herpes simplex virus that synergizes with phosphoinositide 3-kinase/Akt pathway inhibitors to target glioblastoma stem cells. Clin Cancer Res (2011) 17:3686-96. doi:10.1158/1078-0432.CCR-10-3142
117. Tong Y, Zhu W, Huang X, You L, Han X, Yang C, et al. PI3K inhibitor LY294002 inhibits activation of the Akt/mTOR pathway induced by an oncolytic adenovirus expressing TRAIL and sensitizes multiple myeloma cells to the oncolytic virus. Oncol Rep (2014) 31:1581-8. doi:10.3892/or.2014.3020
118. Kaur S, Lal L, Sassano A, Majchrzak-Kita B, Srikanth M, Baker DP, et al. Regulatory effects of mammalian target of rapamycin-activated pathways in type I and II interferon signaling. J Biol Chem (2007) 282:1757-68. doi:10.1074/jbc.M607365200
119. Lukashev AN, Fuerer C, Chen MJ, Searle P, Iggo R. Late expression of nitroreductase in an oncolytic adenovirus sensitizes colon cancer cells to the prodrug CB1954. Hum Gene Ther (2005) 16:1473-83. doi:10.1089/hum.2005.16.1473
120. Jiang ZK, Johnson M, Moughon DL, Kuo J, Sato M, Wu L. Rapamycin enhances adenovirus-mediated cancer imaging and therapy in pre-immunized murine hosts. PLoS One (2013) 8:e73650. doi:10.1371/journal.pone.0073650
121. Fu X, Tao L, Rivera A, Zhang X. Rapamycin enhances the activity of oncolytic herpes simplex virus against tumor cells that are resistant to virus replication. Int J Cancer (2011) 129:1503-10. doi:10.1002/ijc.25808
122. Alain T, Lun X, Martineau Y, Sean P, Pulendran B, Petroulakis E, et al. Vesicular stomatitis virus oncolysis is potentiated by impairing mTORC1-dependent type I IFN production. Proc Natl Acad Sci U S A (2010) 107:1576-81. doi:10.1073/pnas.0912344107
123. Stanford MM, Barrett JW, Nazarian SH, Werden S, Mcfadden G. Oncolytic virotherapy synergism with signaling inhibitors: rapamycin increases myxoma virus tropism for human tumor cells. J Virol (2007) 81:1251-60. doi:10.1128/JVI.01408-06
124. Zemp FJ, Lun X, Mckenzie BA, Zhou H, Maxwell L, Sun B, et al. Treating brain tumor-initiating cells using a combination of myxoma virus and rapamycin. Neuro Oncol (2013) 15:904-20. doi:10.1093/neuonc/not035
125. Diallo JS, Le Boeuf F, Lai F, Cox J, Vaha-Koskela M, Abdelbary H, et al. A high-throughput pharmacoviral approach identifies novel oncolytic virus sensitizers. Mol Ther (2010) 18:1123-9. doi:10.1038/mt.2010.67
126. Kiviharju TM, Lecane PS, Sellers RG, Peehl DM. Antiproliferative and proapoptotic activities of triptolide (PG490), a natural product entering clinical trials, on primary cultures of human prostatic epithelial cells. Clin Cancer Res (2002) 8:2666-74.
127. Kitzen JJ, De Jonge MJ, Lamers CH, Eskens FA, Van Der Biessen D, Van Doorn L, et al. Phase I dose-escalation study of F60008, a novel apoptosis inducer, in patients with advanced solid tumours. Eur J Cancer (2009) 45:1764-72. doi:10.1016/j.ejca.2009.01.026
128. Wong KF, Yuan Y, Luk JM. Tripterygium wilfordii bioactive compounds as anticancer and anti-inflammatory agents. Clin Exp Pharmacol Physiol (2012) 39:311-20. doi:10.1111/j.1440-1681.2011.05586.x
129. Zhou ZL, Yang YX, Ding J, Li YC, Miao ZH. Triptolide: structural modifications, structure-activity relationships, bioactivities, clinical development and mechanisms. Nat Prod Rep (2012) 29:457-75. doi:10.1039/c2np00088a
130. Ben Yebdri F, Van Grevenynghe J, Tang VA, Goulet ML, Wu JH, Stojdl DF, et al. Triptolide-mediated inhibition of interferon signaling enhances vesicular stomatitis virus-based oncolysis. Mol Ther (2013) 21:2043-53. doi:10.1038/mt.2013.187
131. Quintas-Cardama A, Vaddi K, Liu P, Manshouri T, Li J, Scherle PA, et al. Preclinical characterization of the selective JAK1/2 inhibitor INCB018424: therapeutic implications for the treatment of myeloproliferative neoplasms. Blood (2010) 115:3109-17. doi:10.1182/blood-2009-04-214957
132. Mesa RA, Yasothan U, Kirkpatrick P. Ruxolitinib. Nat Rev Drug Discov (2012) 11:103-4. doi:10.1038/nrd3652
133. Quintas-Cardama A, Kantarjian H, Cortes J, Verstovsek S. Janus kinase inhibitors for the treatment of myeloproliferative neoplasias and beyond. Nat Rev Drug Discov (2011) 10:127-40. doi:10.1038/nrd3264
134. Verstovsek S, Kantarjian H, Mesa RA, Pardanani AD, Cortes-Franco J, Thomas DA, et al. Safety and efficacy of INCB018424, a JAK1 and JAK2 inhibitor, in myelofibrosis. N Engl J Med (2010) 363:1117-27. doi:10.1056/NEJMoa1002028
135. Escobar-Zarate D, Liu YP, Suksanpaisan L, Russell SJ, Peng KW. Overcoming cancer cell resistance to VSV oncolysis with JAK1/2 inhibitors. Cancer Gene Ther (2013) 20:582-9. doi:10.1038/cgt.2013.55
136. Paglino JC, van den Pol AN. Vesicular stomatitis virus has extensive oncolytic activity against human sarcomas: rare resistance is overcome by blocking interferon pathways. J Virol (2011) 85:9346-58. doi:10.1128/JVI.00723-11
137. Heinrich B, Goepfert K, Delic M, Galle PR, Moehler M. Influence of the oncolytic parvovirus H-1, CTLA-4 antibody tremelimumab and cytostatic drugs on the human immune system in a human in vitro model of colorectal cancer cells. Onco Targets Ther (2013) 6:1119-27. doi:10.2147/OTT.S49371
138. Zamarin D, Holmgaard RB, Subudhi SK, Park JS, Mansour M, Palese P, et al. Localized oncolytic virotherapy overcomes systemic tumor resistance to immune checkpoint blockade immunotherapy. Sci Transl Med (2014) 6:226ra232. doi:10.1126/scitranslmed.3008095