Oncolytic viruses—immunotherapeutics on the rise

Journal of Molecular Medicine

Volumn 94, Issue 9, 2016, Pages 979-991

  Keller, Brian A ^a,b   Bell, John C ^a,b  

^a OTTAWA HOSPITAL RESEARCH INSTITUTE   (Canada)

^b UNIVERSITY OF OTTAWA   (Canada)

Author keywords

Cancer; Combination therapy; Immune checkpoint inhibitors; Immunotherapy; Oncolytic viruses

Indexed keywords

ANTINEOPLASTIC AGENT; IMMUNE CHECKPOINT INHIBITOR; ONCOLYTIC VIRUS; TALIMOGENE LAHERPAREPVEC; UNCLASSIFIED DRUG; IMMUNOLOGICAL ANTINEOPLASTIC AGENT; TUMOR MARKER;

ADOPTIVE IMMUNOTHERAPY; CANCER IMMUNOTHERAPY; CELL THERAPY; CLINICAL PRACTICE; DRUG POTENTIATION; DRUG SELECTIVITY; HUMAN; MALIGNANT NEOPLASTIC DISEASE; NONHUMAN; ONCOLYTIC VIROTHERAPY; PHARMACEUTICAL ENGINEERING; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); REVIEW; TUMOR IMMUNITY; ADMINISTRATION AND DOSAGE; ANIMAL; CLINICAL TRIAL (TOPIC); DRUG EFFECTS; GENE EXPRESSION; GENE THERAPY; GENE TRANSFER; GENE VECTOR; GENETICS; IMMUNOLOGY; IMMUNOMODULATION; IMMUNOTHERAPY; MOLECULARLY TARGETED THERAPY; MULTIMODALITY CANCER THERAPY; NEOPLASM; PATHOLOGY; PROCEDURES; TRANSGENE; TREATMENT OUTCOME;

ANIMALS; ANTINEOPLASTIC AGENTS, IMMUNOLOGICAL; BIOMARKERS, TUMOR; CLINICAL TRIALS AS TOPIC; COMBINED MODALITY THERAPY; GENE EXPRESSION; GENE TRANSFER TECHNIQUES; GENETIC THERAPY; GENETIC VECTORS; HUMANS; IMMUNOMODULATION; IMMUNOTHERAPY; IMMUNOTHERAPY, ADOPTIVE; MOLECULAR TARGETED THERAPY; NEOPLASMS; ONCOLYTIC VIROTHERAPY; ONCOLYTIC VIRUSES; TRANSGENES; TREATMENT OUTCOME;

EID: 84982958685     PISSN: 09462716     EISSN: 14321440     Source Type: Journal    
DOI: 10.1007/s00109-016-1453-9     Document Type: Review

References (97)

1. Couzin-Frankel J (2013) Breakthrough of the year 2013. Cancer immunotherapy. Science 342:1432–1433
2. Hoos A (2016) Development of immuno-oncology drugs—from CTLA4 to PD1 to the next generations. Nat Rev Drug Discov 15:235–247
3. Sheridan C (2015) IDO inhibitors move center stage in immuno-oncology. Nat Biotechnol 33:321–322
4. Uyttenhove C, Pilotte L, Theate I, Stroobant V, Colau D, Parmentier N, Boon T, Van den Eynde BJ (2003) Evidence for a tumoral immune resistance mechanism based on tryptophan degradation by indoleamine 2,3-dioxygenase. Nat Med 9:1269–1274
5. Topalian SL, Sznol M, McDermott DF, Kluger HM, Carvajal RD, Sharfman WH, Brahmer JR, Lawrence DP, Atkins MB, Powderly JD et al (2014) Survival, durable tumor remission, and long-term safety in patients with advanced melanoma receiving nivolumab. J Clin Oncol 32:1020–1030
6. Ansell SM, Lesokhin AM, Borrello I, Halwani A, Scott EC, Gutierrez M, Schuster SJ, Millenson MM, Cattry D, Freeman GJ et al (2015) PD-1 blockade with nivolumab in relapsed or refractory Hodgkin's lymphoma. N Engl J Med 372:311–319
7. Larkin J, Chiarion-Sileni V, Gonzalez R, Grob JJ, Cowey CL, Lao CD, Schadendorf D, Dummer R, Smylie M, Rutkowski P et al (2015) Combined nivolumab and ipilimumab or monotherapy in untreated melanoma. N Engl J Med 373:23–34
8. Lichty BD, Breitbach CJ, Stojdl DF, Bell JC (2014) Going viral with cancer immunotherapy. Nat Rev Cancer 14:559–567
9. Ivashkiv LB, Donlin LT (2014) Regulation of type I interferon responses. Nat Rev Immunol 14:36–49
10. Sun WH, Pabon C, Alsayed Y, Huang PP, Jandeska S, Uddin S, Platanias LC, Rosen ST (1998) Interferon-alpha resistance in a cutaneous T-cell lymphoma cell line is associated with lack of STAT1 expression. Blood 91:570–576
11. Wong LH, Krauer KG, Hatzinisiriou I, Estcourt MJ, Hersey P, Tam ND, Edmondson S, Devenish RJ, Ralph SJ (1997) Interferon-resistant human melanoma cells are deficient in ISGF3 components, STAT1, STAT2, and p48-ISGF3gamma. J Biol Chem 272:28779–28785
12. Stojdl DF, Lichty B, Knowles S, Marius R, Atkins H, Sonenberg N, Bell JC (2000) Exploiting tumor-specific defects in the interferon pathway with a previously unknown oncolytic virus. Nat Med 6:821–825
13. Pikor LABJC, Diallo J-S (2015) Oncolytic viruses: exploiting Cancer’s deal with the devil. Trends in Cancer 1:266–277
14. Li S, Zhu M, Pan R, Fang T, Cao YY, Chen S, Zhao X, Lei CQ, Guo L, Chen Y et al (2016) The tumor suppressor PTEN has a critical role in antiviral innate immunity. Nat Immunol 17:241–249
15. Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144:646–674
16. Arulanandam R, Batenchuk C, Angarita FA, Ottolino-Perry K, Cousineau S, Mottashed A, Burgess E, Falls TJ, De Silva N, Tsang J et al (2015) VEGF-mediated induction of PRD1-BF1/Blimp1 expression sensitizes tumor vasculature to oncolytic virus infection. Cancer Cell 28:210–224
17. Ilkow CS, Marguerie M, Batenchuk C, Mayer J, Ben Neriah D, Cousineau S, Falls T, Jennings VA, Boileau M, Bellamy D et al (2015) Reciprocal cellular cross-talk within the tumor microenvironment promotes oncolytic virus activity. Nat Med 21:530–536
18. Liu BL, Robinson M, Han ZQ, Branston RH, English C, Reay P, McGrath Y, Thomas SK, Thornton M, Bullock P et al (2003) ICP34.5 deleted herpes simplex virus with enhanced oncolytic, immune stimulating, and anti-tumour properties. Gene Ther 10:292–303
19. Kohlhapp FJ, Kaufman HL (2016) Molecular pathways: mechanism of action for Talimogene Laherparepvec, a new oncolytic virus immunotherapy. Clin Cancer Res 22:1048–1054
20. Dock G (1904) The influence of complicating diseases upon leukemia. The American Journal of Medical Sciences 127:563–592
21. Kelly E, Russell SJ (2007) History of oncolytic viruses: genesis to genetic engineering. Mol Ther 15:651–659
22. Moore AE (1951) The destructive effects of viruses on transplantable mouse tumors. Acta Unio Int Contra Cancrum 7:279–281
23. Hoster HA, Zanes RP Jr, Von Haam E (1949) Studies in Hodgkin’s syndrome; the association of viral hepatitis and Hodgkin’s disease; a preliminary report. Cancer Res 9:473–480
24. Southam CM, Moore AE (1952) Clinical studies of viruses as antineoplastic agents with particular reference to Egypt 101 virus. Cancer 5:1025–1034
25. Asada T (1974) Treatment of human cancer with mumps virus. Cancer 34:1907–1928
26. Liu TC, Galanis E, Kirn D (2007) Clinical trial results with oncolytic virotherapy: a century of promise, a decade of progress. Nat Clin Pract Oncol 4:101–117
27. Parato KA, Senger D, Forsyth PA, Bell JC (2005) Recent progress in the battle between oncolytic viruses and tumours. Nat Rev Cancer 5:965–976
28. Andtbacka RH, Ross M, Puzanov I, Milhem M, Collichio F, Delman KA, Amatruda T, Zager JS, Cranmer L, Hsueh E et al (2016) Patterns of clinical response with Talimogene Laherparepvec (T-VEC) in patients with melanoma treated in the OPTiM phase III clinical trial. Ann Surg Oncol. doi:10.1245/s10434-016-5286-0
29. Andtbacka RH, Kaufman HL, Collichio F, Amatruda T, Senzer N, Chesney J, Delman KA, Spitler LE, Puzanov I, Agarwala SS et al (2015) Talimogene Laherparepvec improves durable response rate in patients with advanced melanoma. J Clin Oncol 33:2780–2788
30. Orvedahl A, Alexander D, Talloczy Z, Sun Q, Wei Y, Zhang W, Burns D, Leib DA, Levine B (2007) HSV-1 ICP34.5 confers neurovirulence by targeting the Beclin 1 autophagy protein. Cell Host Microbe 1:23–35
31. Brown SM, MacLean AR, McKie EA, Harland J (1997) The herpes simplex virus virulence factor ICP34.5 and the cellular protein MyD116 complex with proliferating cell nuclear antigen through the 63-amino-acid domain conserved in ICP34.5, MyD116, and GADD34. J Virol 71:9442–9449
32. Miao L, Fraefel C, Sia KC, Newman JP, Mohamed-Bashir SA, Ng WH, Lam PY (2014) The potential application of a transcriptionally regulated oncolytic herpes simplex virus for human cancer therapy. Br J Cancer 110:94–106
33. Tyminski E, Leroy S, Terada K, Finkelstein DM, Hyatt JL, Danks MK, Potter PM, Saeki Y, Chiocca EA (2005) 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 65:6850–6857
34. Kanai R, Zaupa C, Sgubin D, Antoszczyk SJ, Martuza RL, Wakimoto H, Rabkin SD (2012) Effect of gamma34.5 deletions on oncolytic herpes simplex virus activity in brain tumors. J Virol 86:4420–4431
35. Nettelbeck DM, Rivera AA, Balague C, Alemany R, Curiel DT (2002) Novel oncolytic adenoviruses targeted to melanoma: specific viral replication and cytolysis by expression of E1A mutants from the tyrosinase enhancer/promoter. Cancer Res 62:4663–4670
36. Bofill-De Ros X, Villanueva E, Fillat C (2015) Late-phase miRNA-controlled oncolytic adenovirus for selective killing of cancer cells. Oncotarget 6:6179–6190
37. Johnson TJ, Hoti N, Liu C, Chowdhury WH, Li Y, Zhang Y, Lupold SE, Deweese T, Rodriguez R (2013) Bicalutamide-activated oncolytic adenovirus for the adjuvant therapy of high-risk prostate cancer. Cancer Gene Ther 20:394–402
38. Tseng AW, Chen C, Breslin MB, Lan MS (2016) Tumor-specific promoter-driven adenoviral therapy for insulinoma. Cell Oncol (Dordr) 39:279–286
39. Kim JH, Oh JY, Park BH, Lee DE, Kim JS, Park HE, Roh MS, Je JE, Yoon JH, Thorne SH et al (2006) Systemic armed oncolytic and immunologic therapy for cancer with JX-594, a targeted poxvirus expressing GM-CSF. Mol Ther 14:361–370
40. Parato KA, Breitbach CJ, Le Boeuf F, Wang J, Storbeck C, Ilkow C, Diallo JS, Falls T, Burns J, Garcia V et al (2012) The oncolytic poxvirus JX-594 selectively replicates in and destroys cancer cells driven by genetic pathways commonly activated in cancers. Mol Ther 20:749–758
41. Breitbach CJ, Burke J, Jonker D, Stephenson J, Haas AR, Chow LQ, Nieva J, Hwang TH, Moon A, Patt R et al (2011) Intravenous delivery of a multi-mechanistic cancer-targeted oncolytic poxvirus in humans. Nature 477:99–102
42. McCart JA, Ward JM, Lee J, Hu Y, Alexander HR, Libutti SK, Moss B, Bartlett DL (2001) Systemic cancer therapy with a tumor-selective vaccinia virus mutant lacking thymidine kinase and vaccinia growth factor genes. Cancer Res 61:8751–8757
43. Zeh HJ, Downs-Canner S, McCart JA, Guo ZS, Rao UN, Ramalingam L, Thorne SH, Jones HL, Kalinski P, Wieckowski E et al (2015) First-in-man study of western reserve strain oncolytic vaccinia virus: safety, systemic spread, and antitumor activity. Mol Ther 23:202–214
44. Zhang Q, Liang C, Yu YA, Chen N, Dandekar T, Szalay AA (2009) The highly attenuated oncolytic recombinant vaccinia virus GLV-1h68: comparative genomic features and the contribution of F14.5 L inactivation. Mol Gen Genomics 282:417–435
45. Galanis E, Hartmann LC, Cliby WA, Long HJ, Peethambaram PP, Barrette BA, Kaur JS, Haluska PJ Jr, Aderca I, Zollman PJ et al (2010) Phase I trial of intraperitoneal administration of an oncolytic measles virus strain engineered to express carcinoembryonic antigen for recurrent ovarian cancer. Cancer Res 70:875–882
46. Reddi HV, Madde P, McDonough SJ, Trujillo MA, Morris JC 3rd, Myers RM, Peng KW, Russell SJ, McIver B, Eberhardt NL (2012) Preclinical efficacy of the oncolytic measles virus expressing the sodium iodide symporter in iodine non-avid anaplastic thyroid cancer: a novel therapeutic agent allowing noninvasive imaging and radioiodine therapy. Cancer Gene Ther 19:659–665
47. Coffey MC, Strong JE, Forsyth PA, Lee PW (1998) Reovirus therapy of tumors with activated Ras pathway. Science 282:1332–1334
48. Villalona-Calero MA, Lam E, Otterson GA, Zhao W, Timmons M, Subramaniam D, Hade EM, Gill GM, Coffey M, Selvaggi G et al (2016) Oncolytic reovirus in combination with chemotherapy in metastatic or recurrent non-small cell lung cancer patients with KRAS-activated tumors. Cancer 122:875–883
49. Kolb EA, Sampson V, Stabley D, Walter A, Sol-Church K, Cripe T, Hingorani P, Ahern CH, Weigel BJ, Zwiebel J et al (2015) A phase I trial and viral clearance study of reovirus (Reolysin) in children with relapsed or refractory extra-cranial solid tumors: a Children’s oncology group phase I consortium report. Pediatr Blood Cancer 62:751–758
50. Brun J, McManus D, Lefebvre C, Hu K, Falls T, Atkins H, Bell JC, McCart JA, Mahoney D, Stojdl DF (2010) Identification of genetically modified Maraba virus as an oncolytic rhabdovirus. Mol Ther 18:1440–1449
51. Pol JG, Zhang L, Bridle BW, Stephenson KB, Resseguier J, Hanson S, Chen L, Kazdhan N, Bramson JL, Stojdl DF et al (2014) Maraba virus as a potent oncolytic vaccine vector. Mol Ther 22:420–429
52. Carew JF, Kooby DA, Halterman MW, Kim SH, Federoff HJ, Fong Y (2001) A novel approach to cancer therapy using an oncolytic herpes virus to package amplicons containing cytokine genes. Mol Ther 4:250–256
53. Varghese S, Rabkin SD, Liu R, Nielsen PG, Ipe T, Martuza RL (2006) Enhanced therapeutic efficacy of IL-12, but not GM-CSF, expressing oncolytic herpes simplex virus for transgenic mouse derived prostate cancers. Cancer Gene Ther 13:253–265
54. Antoszczyk S, Spyra M, Mautner VF, Kurtz A, Stemmer-Rachamimov AO, Martuza RL, Rabkin SD (2014) Treatment of orthotopic malignant peripheral nerve sheath tumors with oncolytic herpes simplex virus. Neuro-Oncology 16:1057–1066
55. Stephenson KB, Barra NG, Davies E, Ashkar AA, Lichty BD (2012) Expressing human interleukin-15 from oncolytic vesicular stomatitis virus improves survival in a murine metastatic colon adenocarcinoma model through the enhancement of anti-tumor immunity. Cancer Gene Ther 19:238–246
56. Todo T, Martuza RL, Dallman MJ, Rabkin SD (2001) In situ expression of soluble B7-1 in the context of oncolytic herpes simplex virus induces potent antitumor immunity. Cancer Res 61:153–161
57. Ino Y, Saeki Y, Fukuhara H, Todo T (2006) Triple combination of oncolytic herpes simplex virus-1 vectors armed with interleukin-12, interleukin-18, or soluble B7-1 results in enhanced antitumor efficacy. Clin Cancer Res 12:643–652
58. Fukuhara H, Ino Y, Kuroda T, Martuza RL, Todo T (2005) Triple gene-deleted oncolytic herpes simplex virus vector double-armed with interleukin 18 and soluble B7-1 constructed by bacterial artificial chromosome-mediated system. Cancer Res 65:10663–10668
59. Terada K, Wakimoto H, Tyminski E, Chiocca EA, Saeki Y (2006) Development of a rapid method to generate multiple oncolytic HSV vectors and their in vivo evaluation using syngeneic mouse tumor models. Gene Ther 13:705–714
60. Vlahava VM, Eliopoulos AG, Sourvinos G (2015) CD40 ligand exhibits a direct antiviral effect on herpes simplex virus type-1 infection via a PI3K-dependent, autophagy-independent mechanism. Cell Signal 27:1253–1263
61. Park BH, Hwang T, Liu TC, Sze DY, Kim JS, Kwon HC, Oh SY, Han SY, Yoon JH, Hong SH et al (2008) Use of a targeted oncolytic poxvirus, JX-594, in patients with refractory primary or metastatic liver cancer: a phase I trial. Lancet Oncol 9:533–542
62. Cerullo V, Pesonen S, Diaconu I, Escutenaire S, Arstila PT, Ugolini M, Nokisalmi P, Raki M, Laasonen L, Sarkioja M et al (2010) Oncolytic adenovirus coding for granulocyte macrophage colony-stimulating factor induces antitumoral immunity in cancer patients. Cancer Res 70:4297–4309
63. Fernandez A, Oliver L, Alvarez R, Fernandez LE, Lee KP, Mesa C (2014) Adjuvants and myeloid-derived suppressor cells: enemies or allies in therapeutic cancer vaccination. Hum Vaccin Immunother 10:3251–3260
64. Edukulla R, Woller N, Mundt B, Knocke S, Gurlevik E, Saborowski M, Malek N, Manns MP, Wirth T, Kuhnel F et al (2009) Antitumoral immune response by recruitment and expansion of dendritic cells in tumors infected with telomerase-dependent oncolytic viruses. Cancer Res 69:1448–1458
65. Lapteva N, Aldrich M, Weksberg D, Rollins L, Goltsova T, Chen SY, Huang XF (2009) Targeting the intratumoral dendritic cells by the oncolytic adenoviral vaccine expressing RANTES elicits potent antitumor immunity. J Immunother 32:145–156
66. Post DE, Sandberg EM, Kyle MM, Devi NS, Brat DJ, Xu Z, Tighiouart M, Van Meir EG (2007) Targeted cancer gene therapy using a hypoxia inducible factor dependent oncolytic adenovirus armed with interleukin-4. Cancer Res 67:6872–6881
67. Choi IK, Lee JS, Zhang SN, Park J, Sonn CH, Lee KM, Yun CO (2011) Oncolytic adenovirus co-expressing IL-12 and IL-18 improves tumor-specific immunity via differentiation of T cells expressing IL-12Rbeta2 or IL-18Ralpha. Gene Ther 18:898–909
68. Freytag SO, Zhang Y, Siddiqui F (2015) Preclinical toxicology of oncolytic adenovirus-mediated cytotoxic and interleukin-12 gene therapy for prostate cancer. Mol Ther Oncolytics 2
69. Poutou J, Bunuales M, Gonzalez-Aparicio M, Garcia-Aragoncillo E, Quetglas JI, Casado R, Bravo-Perez C, Alzuguren P, Hernandez-Alcoceba R (2015) Safety and antitumor effect of oncolytic and helper-dependent adenoviruses expressing interleukin-12 variants in a hamster pancreatic cancer model. Gene Ther 22:696–706
70. Kim HS, Kim-Schulze S, Kim DW, Kaufman HL (2009) Host lymphodepletion enhances the therapeutic activity of an oncolytic vaccinia virus expressing 4-1BB ligand. Cancer Res 69:8516–8525
71. Huang JH, Zhang SN, Choi KJ, Choi IK, Kim JH, Lee MG, Kim H, Yun CO (2010) Therapeutic and tumor-specific immunity induced by combination of dendritic cells and oncolytic adenovirus expressing IL-12 and 4-1BBL. Mol Ther 18:264–274
72. John LB, Howland LJ, Flynn JK, West AC, Devaud C, Duong CP, Stewart TJ, Westwood JA, Guo ZS, Bartlett DL et al (2012) Oncolytic virus and anti-4-1BB combination therapy elicits strong antitumor immunity against established cancer. Cancer Res 72:1651–1660
73. Postow MA, Chesney J, Pavlick AC, Robert C, Grossmann K, McDermott D, Linette GP, Meyer N, Giguere JK, Agarwala SS et al (2015) Nivolumab and ipilimumab versus ipilimumab in untreated melanoma. N Engl J Med 372:2006–2017
74. Robert C, Schachter J, Long GV, Arance A, Grob JJ, Mortier L, Daud A, Carlino MS, McNeil C, Lotem M et al (2015) Pembrolizumab versus ipilimumab in advanced melanoma. N Engl J Med 372:2521–2532
75. Zamarin D, Holmgaard RB, Subudhi SK, Park JS, Mansour M, Palese P, Merghoub T, Wolchok JD, Allison JP (2014) Localized oncolytic virotherapy overcomes systemic tumor resistance to immune checkpoint blockade immunotherapy. Sci Transl Med 6:226ra232
76. Quetglas JI, Labiano S, Aznar MA, Bolanos E, Azpilikueta A, Rodriguez I, Casales E, Sanchez-Paulete AR, Segura V, Smerdou C et al (2015) Virotherapy with a Semliki Forest virus-based vector encoding IL12 synergizes with PD-1/PD-L1 blockade. Cancer Immunol Res 3:449–454
77. Puzanov I, Milhem MM, Minor D, Hamid O, Li A, Chen L, Chastain M, Gorski KS, Anderson A, Chou J et al (2016) Talimogene Laherparepvec in combination with ipilimumab in previously untreated, unresectable stage IIIB-IV melanoma. J Clin Oncol 34:2619–2626
78. Chow LQ (2013) Exploring novel immune-related toxicities and endpoints with immune-checkpoint inhibitors in non-small cell lung cancer. Am Soc Clin Oncol Educ Book. doi:10.1200/EdBook_AM.2013.33.e280
79. Spain L, Diem S, Larkin J (2016) Management of toxicities of immune checkpoint inhibitors. Cancer Treat Rev 44:51–60
80. Dias JD, Hemminki O, Diaconu I, Hirvinen M, Bonetti A, Guse K, Escutenaire S, Kanerva A, Pesonen S, Loskog A et al (2012) Targeted cancer immunotherapy with oncolytic adenovirus coding for a fully human monoclonal antibody specific for CTLA-4. Gene Ther 19:988–998
81. Du T, Shi G, Li YM, Zhang JF, Tian HW, Wei YQ, Deng H, Yu DC (2014) Tumor-specific oncolytic adenoviruses expressing granulocyte macrophage colony-stimulating factor or anti-CTLA4 antibody for the treatment of cancers. Cancer Gene Ther 21:340–348
82. Engeland CE, Grossardt C, Veinalde R, Bossow S, Lutz D, Kaufmann JK, Shevchenko I, Umansky V, Nettelbeck DM, Weichert W et al (2014) CTLA-4 and PD-L1 checkpoint blockade enhances oncolytic measles virus therapy. Mol Ther 22:1949–1959
83. Rosenberg SA (2011) Cell transfer immunotherapy for metastatic solid cancer—what clinicians need to know. Nat Rev Clin Oncol 8:577–585
84. Restifo NP, Dudley ME, Rosenberg SA (2012) Adoptive immunotherapy for cancer: harnessing the T cell response. Nat Rev Immunol 12:269–281
85. Qiao J, Kottke T, Willmon C, Galivo F, Wongthida P, Diaz RM, Thompson J, Ryno P, Barber GN, Chester J et al (2008) Purging metastases in lymphoid organs using a combination of antigen-nonspecific adoptive T cell therapy, oncolytic virotherapy and immunotherapy. Nat Med 14:37–44
86. Qiao J, Wang H, Kottke T, Diaz RM, Willmon C, Hudacek A, Thompson J, Parato K, Bell J, Naik J et al (2008) Loading of oncolytic vesicular stomatitis virus onto antigen-specific T cells enhances the efficacy of adoptive T-cell therapy of tumors. Gene Ther 15:604–616
87. Pfirschke C, Schirrmacher V (2009) Cross-infection of tumor cells by contact with T lymphocytes loaded with Newcastle disease virus. Int J Oncol 34:951–962
88. Grekova S, Aprahamian M, Giese N, Schmitt S, Giese T, Falk CS, Daeffler L, Cziepluch C, Rommelaere J, Raykov Z (2010) Immune cells participate in the oncosuppressive activity of parvovirus H-1PV and are activated as a result of their abortive infection with this agent. Cancer Biol Ther 10:1280–1289
89. Yan Y, Li S, Jia T, Du X, Xu Y, Zhao Y, Li L, Liang K, Liang W, Sun H et al (2015) Combined therapy with CTL cells and oncolytic adenovirus expressing IL-15-induced enhanced antitumor activity. Tumour Biol 36:4535–4543
90. Yan Y, Xu Y, Zhao Y, Li L, Sun P, Liu H, Fan Q, Liang K, Liang W, Sun H et al (2014) Combination of E2F-1 promoter-regulated oncolytic adenovirus and cytokine-induced killer cells enhances the antitumor effects in an orthotopic rectal cancer model. Tumour Biol 35:1113–1122
91. Hu H, Qiu Y, Guo M, Huang Y, Fang L, Peng Z, Ji W, Xu Y, Shen S, Yan Y et al (2015) Targeted Hsp70 expression combined with CIK-activated immune reconstruction synergistically exerts antitumor efficacy in patient-derived hepatocellular carcinoma xenograft mouse models. Oncotarget 6:1079–1089
92. Yang Z, Zhang Q, Xu K, Shan J, Shen J, Liu L, Xu Y, Xia F, Bie P, Zhang X et al (2012) Combined therapy with cytokine-induced killer cells and oncolytic adenovirus expressing IL-12 induce enhanced antitumor activity in liver tumor model. PLoS One 7:e44802
93. Pittari G, Filippini P, Gentilcore G, Grivel JC, Rutella S (2015) Revving up natural killer cells and cytokine-induced killer cells against hematological malignancies. Front Immunol 6:230
94. Fu X, Rivera A, Tao L, Zhang X (2015) An HSV-2 based oncolytic virus can function as an attractant to guide migration of adoptively transferred T cells to tumor sites. Oncotarget 6:902–914
95. Nishio N, Diaconu I, Liu H, Cerullo V, Caruana I, Hoyos V, Bouchier-Hayes L, Savoldo B, Dotti G (2014) Armed oncolytic virus enhances immune functions of chimeric antigen receptor-modified T cells in solid tumors. Cancer Res 74:5195–5205
96. Singh P, Pal SK, Alex A, Agarwal N (2015) Development of PROSTVAC immunotherapy in prostate cancer. Future Oncol 11:2137–2148
97. Evgin L, Acuna SA, Tanese de Souza C, Marguerie M, Lemay CG, Ilkow CS, Findlay CS, Falls T, Parato KA, Hanwell D et al (2015) Complement inhibition prevents oncolytic vaccinia virus neutralization in immune humans and cynomolgus macaques. Mol Ther 23:1066–1076