Harnessing the Power of Onco-Immunotherapy with Checkpoint Inhibitors

Karishma R Rajani, Richard G Vile, Karishma R Rajani, Richard G Vile

Abstract

Oncolytic viruses represent a diverse class of replication competent viruses that curtail tumor growth. These viruses, through their natural ability or through genetic modifications, can selectively replicate within tumor cells and induce cell death while leaving normal cells intact. Apart from the direct oncolytic activity, these viruses mediate tumor cell death via the induction of innate and adaptive immune responses. The field of oncolytic viruses has seen substantial advancement with the progression of numerous oncolytic viruses in various phases of clinical trials. Tumors employ a plethora of mechanisms to establish growth and subsequently metastasize. These include evasion of immune surveillance by inducing up-regulation of checkpoint proteins which function to abrogate T cell effector functions. Currently, antibodies blocking checkpoint proteins such as anti-cytotoxic T-lymphocyte antigen-4 (CTLA-4) and anti-programmed cell death-1 (PD-1) have been approved to treat cancer and shown to impart durable clinical responses. These antibodies typically need pre-existing active immune tumor microenvironment to establish durable clinical outcomes and not every patient responds to these therapies. This review provides an overview of published pre-clinical studies demonstrating superior therapeutic efficacy of combining oncolytic viruses with checkpoint blockade compared to monotherapies. These studies provide compelling evidence that oncolytic therapy can be potentiated by coupling it with checkpoint therapies.

Keywords: anti-CTLA-4; anti-PD-1; checkpoint inhibitors; immune-evasion; immunotherapy; innate and adaptive immunity; oncoimmunotherapy; oncolytic viruses.

References

    1. Russell S.J., Peng K.W., Bell J.C. Oncolytic virotherapy. Nat. Biotechnol. 2012;30:658–670. doi: 10.1038/nbt.2287.
    1. Guo Z.S., Liu Z., Bartlett D.L. Oncolytic Immunotherapy: Dying the Right Way is a Key to Eliciting Potent Antitumor Immunity. Front. Oncol. 2014;4:74. doi: 10.3389/fonc.2014.00074.
    1. Green D.R., Ferguson T., Zitvogel L., Kroemer G. Immunogenic and tolerogenic cell death. Nat. Rev. Immunol. 2009;9:353–363. doi: 10.1038/nri2545.
    1. Lichty B.D., Breitbach C.J., Stojdl D.F., Bell J.C. Going viral with cancer immunotherapy. Nat. Rev. Cancer. 2014;14:559–567. doi: 10.1038/nrc3770.
    1. Diaz R.M., Galivo F., Kottke T., Wongthida P., Qiao J., Thompson J., Valdes M., Barber G., Vile R.G. Oncolytic immunovirotherapy for melanoma using vesicular stomatitis virus. Cancer Res. 2007;67:2840–2848. doi: 10.1158/0008-5472.CAN-06-3974.
    1. Todo T. “Armed” oncolytic herpes simplex viruses for brain tumor therapy. Cell Adhes. Migr. 2008;2:208–213. doi: 10.4161/cam.2.3.6353.
    1. Prestwich R.J., Ilett E.J., Errington F., Diaz R.M., Steele L.P., Kottke T., Thompson J., Galivo F., Harrington K.J., Pandha H.S., et al. Immune-mediated antitumor activity of reovirus is required for therapy and is independent of direct viral oncolysis and replication. Clin. Cancer Res. Off. J. Am. Assoc. Cancer Res. 2009;15:4374–4381. doi: 10.1158/1078-0432.CCR-09-0334.
    1. Hanahan D., Weinberg R.A. Hallmarks of cancer: The next generation. Cell. 2011;144:646–674. doi: 10.1016/j.cell.2011.02.013.
    1. Drake C.G., Jaffee E., Pardoll D.M. Mechanisms of immune evasion by tumors. Adv. Immunol. 2006;90:51–81.
    1. Marincola F.M., Jaffee E.M., Hicklin D.J., Ferrone S. Escape of human solid tumors from T-cell recognition: Molecular mechanisms and functional significance. Adv. Immunol. 2000;74:181–273.
    1. Kim R., Emi M., Tanabe K. Cancer immunoediting from immune surveillance to immune escape. Immunology. 2007;121:1–14. doi: 10.1111/j.1365-2567.2007.02587.x.
    1. Li M.O., Wan Y.Y., Sanjabi S., Robertson A.K., Flavell R.A. Transforming growth factor-beta regulation of immune responses. Annu. Rev. Immunol. 2006;24:99–146. doi: 10.1146/annurev.immunol.24.021605.090737.
    1. Jones E., Dahm-Vicker M., Golgher D., Gallimore A. CD25+ regulatory T cells and tumor immunity. Immunol. Lett. 2003;85:141–143. doi: 10.1016/S0165-2478(02)00240-7.
    1. Orentas R.J., Kohler M.E., Johnson B.D. Suppression of anti-cancer immunity by regulatory T cells: Back to the future. Semin. Cancer Biol. 2006;16:137–149. doi: 10.1016/j.semcancer.2005.11.007.
    1. Talmadge J.E., Gabrilovich D.I. History of myeloid-derived suppressor cells. Nat. Rev. Cancer. 2013;13:739–752. doi: 10.1038/nrc3581.
    1. Chambers C.A., Kuhns M.S., Egen J.G., Allison J.P. CTLA-4-mediated inhibition in regulation of T cell responses: Mechanisms and manipulation in tumor immunotherapy. Annu. Rev. Immunol. 2001;19:565–594. doi: 10.1146/annurev.immunol.19.1.565.
    1. Keir M.E., Butte M.J., Freeman G.J., Sharpe A.H. PD-1 and its ligands in tolerance and immunity. Annu. Rev. Immunol. 2008;26:677–704. doi: 10.1146/annurev.immunol.26.021607.090331.
    1. Kahan S.M., Wherry E.J., Zajac A.J. T cell exhaustion during persistent viral infections. Virology. 2015;479–480:180–193. doi: 10.1016/j.virol.2014.12.033.
    1. Freeman G.J., Long A.J., Iwai Y., Bourque K., Chernova T., Nishimura H., Fitz L.J., Malenkovich N., Okazaki T., Byrne M.C., et al. Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation. J. Exp. Med. 2000;192:1027–1034. doi: 10.1084/jem.192.7.1027.
    1. Leach D.R., Krummel M.F., Allison J.P. Enhancement of antitumor immunity by CTLA-4 blockade. Science. 1996;271:1734–1736. doi: 10.1126/science.271.5256.1734.
    1. Zhu C., Anderson A.C., Schubart A., Xiong H., Imitola J., Khoury S.J., Zheng X.X., Strom T.B., Kuchroo V.K. The Tim-3 ligand galectin-9 negatively regulates T helper type 1 immunity. Nat. Immunol. 2005;6:1245–1252. doi: 10.1038/ni1271.
    1. Grosso J.F., Kelleher C.C., Harris T.J., Maris C.H., Hipkiss E.L., de Marzo A., Anders R., Netto G., Getnet D., Bruno T.C., et al. LAG-3 regulates CD8+ T cell accumulation and effector function in murine self- and tumor-tolerance systems. J. Clin. Investig. 2007;117:3383–3392. doi: 10.1172/JCI31184.
    1. Huang C.T., Workman C.J., Flies D., Pan X., Marson A.L., Zhou G., Hipkiss E.L., Ravi S., Kowalski J., Levitsky H.I., et al. Role of LAG-3 in regulatory T cells. Immunity. 2004;21:503–513. doi: 10.1016/j.immuni.2004.08.010.
    1. Phan G.Q., Yang J.C., Sherry R.M., Hwu P., Topalian S.L., Schwartzentruber D.J., Restifo N.P., Haworth L.R., Seipp C.A., Freezer L.J., et al. Cancer regression and autoimmunity induced by cytotoxic T lymphocyte-associated antigen 4 blockade in patients with metastatic melanoma. Proc. Natl. Acad. Sci. USA. 2003;100:8372–8377. doi: 10.1073/pnas.1533209100.
    1. Nishimura H., Nose M., Hiai H., Minato N., Honjo T. Development of lupus-like autoimmune diseases by disruption of the PD-1 gene encoding an ITIM motif-carrying immunoreceptor. Immunity. 1999;11:141–151. doi: 10.1016/S1074-7613(00)80089-8.
    1. Tivol E.A., Borriello F., Schweitzer A.N., Lynch W.P., Bluestone J.A., Sharpe A.H. Loss of CTLA-4 leads to massive lymphoproliferation and fatal multiorgan tissue destruction, revealing a critical negative regulatory role of CTLA-4. Immunity. 1995;3:541–547. doi: 10.1016/1074-7613(95)90125-6.
    1. Pardoll D.M. The blockade of immune checkpoints in cancer immunotherapy. Nat. Rev. Cancer. 2012;12:252–264. doi: 10.1038/nrc3239.
    1. Parry R.V., Chemnitz J.M., Frauwirth K.A., Lanfranco A.R., Braunstein I., Kobayashi S.V., Linsley P.S., Thompson C.B., Riley J.L. CTLA-4 and PD-1 receptors inhibit T-cell activation by distinct mechanisms. Mol. Cell. Biol. 2005;25:9543–9553. doi: 10.1128/MCB.25.21.9543-9553.2005.
    1. Collins A.V., Brodie D.W., Gilbert R.J., Iaboni A., Manso-Sancho R., Walse B., Stuart D.I., van der Merwe P.A., Davis S.J. The interaction properties of costimulatory molecules revisited. Immunity. 2002;17:201–210. doi: 10.1016/S1074-7613(02)00362-X.
    1. Egen J.G., Allison J.P. Cytotoxic T lymphocyte antigen-4 accumulation in the immunological synapse is regulated by TCR signal strength. Immunity. 2002;16:23–35. doi: 10.1016/S1074-7613(01)00259-X.
    1. Darlington P.J., Baroja M.L., Chau T.A., Siu E., Ling V., Carreno B.M., Madrenas J. Surface cytotoxic T lymphocyte-associated antigen 4 partitions within lipid rafts and relocates to the immunological synapse under conditions of inhibition of T cell activation. J. Exp. Med. 2002;195:1337–1347. doi: 10.1084/jem.20011868.
    1. Linsley P.S., Bradshaw J., Greene J., Peach R., Bennett K.L., Mittler R.S. Intracellular trafficking of CTLA-4 and focal localization towards sites of TCR engagement. Immunity. 1996;4:535–543. doi: 10.1016/S1074-7613(00)80480-X.
    1. Linsley P.S., Greene J.L., Brady W., Bajorath J., Ledbetter J.A., Peach R. Human B7-1 (CD80) and B7-2 (CD86) bind with similar avidities but distinct kinetics to CD28 and CTLA-4 receptors. Immunity. 1994;1:793–801. doi: 10.1016/S1074-7613(94)80021-9.
    1. Schneider H., Downey J., Smith A., Zinselmeyer B.H., Rush C., Brewer J.M., Wei B., Hogg N., Garside P., Rudd C.E. Reversal of the TCR stop signal by CTLA-4. Science. 2006;313:1972–1975. doi: 10.1126/science.1131078.
    1. Riley J.L., Mao M., Kobayashi S., Biery M., Burchard J., Cavet G., Gregson B.P., June C.H., Linsley P.S. Modulation of TCR-induced transcriptional profiles by ligation of CD28, ICOS, and CTLA-4 receptors. Proc. Natl. Acad. Sci. USA. 2002;99:11790–11795. doi: 10.1073/pnas.162359999.
    1. Peggs K.S., Quezada S.A., Chambers C.A., Korman A.J., Allison J.P. Blockade of CTLA-4 on both effector and regulatory T cell compartments contributes to the antitumor activity of anti-CTLA-4 antibodies. J. Exp. Med. 2009;206:1717–1725. doi: 10.1084/jem.20082492.
    1. Takahashi T., Tagami T., Yamazaki S., Uede T., Shimizu J., Sakaguchi N., Mak T.W., Sakaguchi S. Immunologic self-tolerance maintained by CD25(+)CD4(+) regulatory T cells constitutively expressing cytotoxic T lymphocyte-associated antigen 4. J. Exp. Med. 2000;192:303–310. doi: 10.1084/jem.192.2.303.
    1. Latchman Y., Wood C.R., Chernova T., Chaudhary D., Borde M., Chernova I., Iwai Y., Long A.J., Brown J.A., Nunes R., et al. PD-L2 is a second ligand for PD-1 and inhibits T cell activation. Nat. Immunol. 2001;2:261–268. doi: 10.1038/85330.
    1. Dong H., Strome S.E., Salomao D.R., Tamura H., Hirano F., Flies D.B., Roche P.C., Lu J., Zhu G., Tamada K., et al. Tumor-associated B7-H1 promotes T-cell apoptosis: A potential mechanism of immune evasion. Nat. Med. 2002;8:793–800. doi: 10.1038/nm0902-1039c.
    1. Rosenwald A., Wright G., Leroy K., Yu X., Gaulard P., Gascoyne R.D., Chan W.C., Zhao T., Haioun C., Greiner T.C., et al. Molecular diagnosis of primary mediastinal B cell lymphoma identifies a clinically favorable subgroup of diffuse large B cell lymphoma related to Hodgkin lymphoma. J. Exp. Med. 2003;198:851–862. doi: 10.1084/jem.20031074.
    1. Ahmadzadeh M., Johnson L.A., Heemskerk B., Wunderlich J.R., Dudley M.E., White D.E., Rosenberg S.A. Tumor antigen-specific CD8 T cells infiltrating the tumor express high levels of PD-1 and are functionally impaired. Blood. 2009;114:1537–1544. doi: 10.1182/blood-2008-12-195792.
    1. Francisco L.M., Sage P.T., Sharpe A.H. The PD-1 pathway in tolerance and autoimmunity. Immunol. Rev. 2010;236:219–242. doi: 10.1111/j.1600-065X.2010.00923.x.
    1. Appleman L.J., van Puijenbroek A.A., Shu K.M., Nadler L.M., Boussiotis V.A. CD28 costimulation mediates down-regulation of p27kip1 and cell cycle progression by activation of the PI3K/PKB signaling pathway in primary human T cells. J. Immunol. 2002;168:2729–2736. doi: 10.4049/jimmunol.168.6.2729.
    1. Datta S.R., Brunet A., Greenberg M.E. Cellular survival: A play in three Akts. Genes Dev. 1999;13:2905–2927. doi: 10.1101/gad.13.22.2905.
    1. Chemnitz J.M., Parry R.V., Nichols K.E., June C.H., Riley J.L. SHP-1 and SHP-2 associate with immunoreceptor tyrosine-based switch motif of programmed death 1 upon primary human T cell stimulation, but only receptor ligation prevents T cell activation. J. Immunol. 2004;173:945–954. doi: 10.4049/jimmunol.173.2.945.
    1. Lee K.M., Chuang E., Griffin M., Khattri R., Hong D.K., Zhang W., Straus D., Samelson L.E., Thompson C.B., Bluestone J.A. Molecular basis of T cell inactivation by CTLA-4. Science. 1998;282:2263–2266. doi: 10.1126/science.282.5397.2263.
    1. Van Elsas A., Hurwitz A.A., Allison J.P. Combination immunotherapy of B16 melanoma using anti-cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) and granulocyte/macrophage colony-stimulating factor (GM-CSF)-producing vaccines induces rejection of subcutaneous and metastatic tumors accompanied by autoimmune depigmentation. J. Exp. Med. 1999;190:355–366.
    1. Zeng J., See A.P., Phallen J., Jackson C.M., Belcaid Z., Ruzevick J., Durham N., Meyer C., Harris T.J., Albesiano E., et al. Anti-PD-1 blockade and stereotactic radiation produce long-term survival in mice with intracranial gliomas. Int. J. Radiat. Oncol. Biol. Phys. 2013;86:343–349. doi: 10.1016/j.ijrobp.2012.12.025.
    1. Naidoo J., Page D.B., Wolchok J.D. Immune modulation for cancer therapy. Br. J. Cancer. 2014;111:2214–2219. doi: 10.1038/bjc.2014.348.
    1. Brahmer J.R., Drake C.G., Wollner I., Powderly J.D., Picus J., Sharfman W.H., Stankevich E., Pons A., Salay T.M., McMiller T.L., et al. Phase I study of single-agent anti-programmed death-1 (MDX-1106) in refractory solid tumors: Safety, clinical activity, pharmacodynamics, and immunologic correlates. J. Clin. Oncol. 2010;28:3167–3175. doi: 10.1200/JCO.2009.26.7609.
    1. Brahmer J.R., Tykodi S.S., Chow L.Q., Hwu W.J., Topalian S.L., Hwu P., Drake C.G., Camacho L.H., Kauh J., Odunsi K., et al. Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N. Engl. J. Med. 2012;366:2455–2465. doi: 10.1056/NEJMoa1200694.
    1. Topalian S.L., Hodi F.S., Brahmer J.R., Gettinger S.N., Smith D.C., McDermott D.F., Powderly J.D., Carvajal R.D., Sosman J.A., Atkins M.B., et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N. Engl. J. Med. 2012;366:2443–2454. doi: 10.1056/NEJMoa1200690.
    1. Van den Eertwegh A.J., Versluis J., van den Berg H.P., Santegoets S.J., van Moorselaar R.J., van der Sluis T.M., Gall H.E., Harding T.C., Jooss K., Lowy I., et al. Combined immunotherapy with granulocyte-macrophage colony-stimulating factor-transduced allogeneic prostate cancer cells and ipilimumab in patients with metastatic castration-resistant prostate cancer: A phase 1 dose-escalation trial. Lancet Oncol. 2012;13:509–517. doi: 10.1016/S1470-2045(12)70007-4.
    1. Powles T., Eder J.P., Fine G.D., Braiteh F.S., Loriot Y., Cruz C., Bellmunt J., Burris H.A., Petrylak D.P., Teng S.L., et al. MPDL3280A (anti-PD-L1) treatment leads to clinical activity in metastatic bladder cancer. Nature. 2014;515:558–562. doi: 10.1038/nature13904.
    1. Herbst R.S., Soria J.C., Kowanetz M., Fine G.D., Hamid O., Gordon M.S., Sosman J.A., McDermott D.F., Powderly J.D., Gettinger S.N., et al. Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients. Nature. 2014;515:563–567. doi: 10.1038/nature14011.
    1. Tumeh P.C., Harview C.L., Yearley J.H., Shintaku I.P., Taylor E.J., Robert L., Chmielowski B., Spasic M., Henry G., Ciobanu V., et al. PD-1 blockade induces responses by inhibiting adaptive immune resistance. Nature. 2014;515:568–571. doi: 10.1038/nature13954.
    1. Ji R.R., Chasalow S.D., Wang L., Hamid O., Schmidt H., Cogswell J., Alaparthy S., Berman D., Jure-Kunkel M., Siemers N.O., et al. An immune-active tumor microenvironment favors clinical response to ipilimumab. Cancer Immunol. Immunother. CII. 2012;61:1019–1031. doi: 10.1007/s00262-011-1172-6.
    1. Curran M.A., Montalvo W., Yagita H., Allison J.P. PD-1 and CTLA-4 combination blockade expands infiltrating T cells and reduces regulatory T and myeloid cells within B16 melanoma tumors. Proc. Natl. Acad. Sci. USA. 2010;107:4275–4280. doi: 10.1073/pnas.0915174107.
    1. Wolchok J.D., Kluger H., Callahan M.K., Postow M.A., Rizvi N.A., Lesokhin A.M., Segal N.H., Ariyan C.E., Gordon R.A., Reed K., et al. Nivolumab plus ipilimumab in advanced melanoma. N. Engl. J. Med. 2013;369:122–133. doi: 10.1056/NEJMoa1302369.
    1. Hammers H.J., Infante E.R.P.J.R., Rini B.I., McDermott D.F., Ernstoff M., Voss M.H., Sharma P., Pal S.K., Razak A.R.A., Kollmannsberger C.K., et al. Expanded Cohort Results from CheckMate 016: A Phase I Study of Nivolumab in Combination with Ipilimumab in Metastatic Renal Cell Carcinoma (mRCC) ASCO; Chicago, IL, USA: 2015.
    1. Postow M.A., Chesney J., Pavlick A.C., Robert C., Grossmann K., McDermott D., Linette G.P., Meyer N., Giguere J.K., Agarwala S.S., et al. Nivolumab and ipilimumab versus ipilimumab in untreated melanoma. N. Engl. J. Med. 2015;372:2006–2017. doi: 10.1056/NEJMoa1414428.
    1. Zamarin D., Holmgaard R.B., Subudhi S.K., Park J.S., Mansour M., Palese P., Merghoub T., Wolchok J.D., Allison J.P. Localized oncolytic virotherapy overcomes systemic tumor resistance to immune checkpoint blockade immunotherapy. Sci. Transl. Med. 2014;6:226ra32. doi: 10.1126/scitranslmed.3008095.
    1. Taube J.M., Anders R.A., Young G.D., Xu H., Sharma R., McMiller T.L., Chen S., Klein A.P., Pardoll D.M., Topalian S.L., et al. Colocalization of inflammatory response with B7-h1 expression in human melanocytic lesions supports an adaptive resistance mechanism of immune escape. Sci. Transl. Med. 2012;4:127ra37. doi: 10.1126/scitranslmed.3003689.
    1. Winograd R., Byrne K.T., Evans R.A., Odorizzi P.M., Meyer A.R., Bajor D.L., Clendenin C., Stanger B.Z., Furth E.E., Wherry E.J., et al. Induction of T-cell Immunity Overcomes Complete Resistance to PD-1 and CTLA-4 Blockade and Improves Survival in Pancreatic Carcinoma. Cancer Immunol. Res. 2015;3:399–411. doi: 10.1158/2326-6066.CIR-14-0215.
    1. Gajewski T.F., Woo S.R., Zha Y., Spaapen R., Zheng Y., Corrales L., Spranger S. Cancer immunotherapy strategies based on overcoming barriers within the tumor microenvironment. Curr. Opin. Immunol. 2013;25:268–276. doi: 10.1016/j.coi.2013.02.009.
    1. Snyder A., Makarov V., Merghoub T., Yuan J., Zaretsky J.M., Desrichard A., Walsh L.A., Postow M.A., Wong P., Ho T.S., et al. Genetic basis for clinical response to CTLA-4 blockade in melanoma. N. Engl. J. Med. 2014;371:2189–2199. doi: 10.1056/NEJMoa1406498.
    1. Piasecki P., Tiep L., Ponce R., Beers C. Talilmogene Laherparepvec Increases the Anti-Tumor Efficacy of the Anti-PD-1 Immune Checkpoint Blockade. AACR; Philadelphia, PA, USA: 2015.
    1. Fiola C., Peeters B., Fournier P., Arnold A., Bucur M., Schirrmacher V. Tumor selective replication of Newcastle disease virus: Association with defects of tumor cells in antiviral defence. Int. J. Cancer. 2006;119:328–338. doi: 10.1002/ijc.21821.
    1. Zamarin D., Palese P. Oncolytic Newcastle disease virus for cancer therapy: Old challenges and new directions. Future Microbiol. 2012;7:347–367. doi: 10.2217/fmb.12.4.
    1. Rojas J., Sampath P., Hou W., Thorne S.H. Defining Effective Combinations of Immune Checkpoint Blockade and Oncolytic Virotherapy. Clin. Cancer Res. Off. J. Am. Assoc. Cancer Res. 2015 doi: 10.1158/1078-0432.CCR-14-2009.
    1. Chan W.M., McFadden G. Oncolytic Poxviruses. Annu. Rev. Virol. 2014;1:119–141. doi: 10.1146/annurev-virology-031413-085442.
    1. McCart J.A., Ward J.M., Lee J., Hu Y., Alexander H.R., Libutti S.K., Moss B., Bartlett D.L. Systemic cancer therapy with a tumor-selective vaccinia virus mutant lacking thymidine kinase and vaccinia growth factor genes. Cancer Res. 2001;61:8751–8757.
    1. Kim J.H., Oh J.Y., Park B.H., Lee D.E., Kim J.S., Park H.E., Roh M.S., Je J.E., Yoon J.H., Thorne S.H., et al. Systemic armed oncolytic and immunologic therapy for cancer with JX-594, a targeted poxvirus expressing GM-CSF. Mol. Ther. J. Am. Soc. Gene Ther. 2006;14:361–370. doi: 10.1016/j.ymthe.2006.05.008.
    1. Heo J., Reid T., Ruo L., Breitbach C.J., Rose S., Bloomston M., Cho M., Lim H.Y., Chung H.C., Kim C.W., et al. Randomized dose-finding clinical trial of oncolytic immunotherapeutic vaccinia JX-594 in liver cancer. Nat. Med. 2013;19:329–336. doi: 10.1038/nm.3089.
    1. Park B.H., Hwang T., Liu T.C., Sze D.Y., Kim J.S., Kwon H.C., Oh S.Y., Han S.Y., Yoon J.H., Hong S.H., 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;9:533–542. doi: 10.1016/S1470-2045(08)70107-4.
    1. Barber G.N. Vesicular stomatitis virus as an oncolytic vector. Viral Immunol. 2004;17:516–527. doi: 10.1089/vim.2004.17.516.
    1. National Cancer Institute, M.C. Viral Therapy in Treating Patient with Liver Cancer. National Library of Medicine; Bethesda, MD, USA: 2012. [(accessed on 5 June 2015)]. Available online: .
    1. Gao Y., Whitaker-Dowling P., Griffin J.A., Barmada M.A., Bergman I. Recombinant vesicular stomatitis virus targeted to Her2/neu combined with anti-CTLA4 antibody eliminates implanted mammary tumors. Cancer Gene Ther. 2009;16:44–52. doi: 10.1038/cgt.2008.55.
    1. Kottke T., Errington F., Pulido J., Galivo F., Thompson J., Wongthida P., Diaz R.M., Chong H., Ilett E., Chester J., et al. Broad antigenic coverage induced by vaccination with virus-based cDNA libraries cures established tumors. Nat. Med. 2011;17:854–859. doi: 10.1038/nm.2390.
    1. Pulido J., Kottke T., Thompson J., Galivo F., Wongthida P., Diaz R.M., Rommelfanger D., Ilett E., Pease L., Pandha H., et al. Using virally expressed melanoma cDNA libraries to identify tumor-associated antigens that cure melanoma. Nat. Biotechnol. 2012;30:337–343. doi: 10.1038/nbt.2157.
    1. Alonso-Camino V., Rajani K., Kottke T., Rommelfanger-Konkol D., Zaidi S., Thompson J., Pulido J., Ilett E., Donnelly O., Selby P., et al. The profile of tumor antigens which can be targeted by immunotherapy depends upon the tumor's anatomical site. Mol. Ther. J. Am. Soc. Gene Ther. 2014;22:1936–1948. doi: 10.1038/mt.2014.134.
    1. Cockle J.V.R.K., Zaidi S., Kottke T., Thompson J., Diaz R., Shim K.S., Peterson T., Parney I., Short S., Selby P., et al. Combination Viroimmunotherapy with Checkpoint Inhibition to Treat Glioma, based on Location-Specific Tumor Profiling. Neuro Oncol. 2015 doi: 10.1093/neuonc/nov173.
    1. Msaouel P., Iankov I.D., Dispenzieri A., Galanis E. Attenuated oncolytic measles virus strains as cancer therapeutics. Curr. Pharm. Biotechnol. 2012;13:1732–1741. doi: 10.2174/138920112800958896.
    1. National Cancer Institute, M.C. Viral Therapy in Treating Patients with Recurrent Glioblastoma Multiforme. National Library of Medicine; Bethesda, MD, USA: 2006. [(accessed on 5 June 2015)]. Available online: .
    1. National Cancer Institute, M.C. MV-NIS or Investigator’s Choice Chemotherapy in Treating Patients with Ovarian, Fallopian, or Peritoneal Cancer. National Library of Medicine; Bethesda, MD, USA: 2015. [(accessed on 10 June 2015)]. Available online: .
    1. Engeland C.E., Grossardt C., Veinalde R., Bossow S., Lutz D., Kaufmann J.K., Shevchenko I., Umansky V., Nettelbeck D.M., Weichert W., et al. CTLA-4 and PD-L1 checkpoint blockade enhances oncolytic measles virus therapy. Mol. Ther. J. Am. Soc. Gene Ther. 2014;22:1949–1959. doi: 10.1038/mt.2014.160.
    1. Errington F., Steele L., Prestwich R., Harrington K.J., Pandha H.S., Vidal L., de Bono J., Selby P., Coffey M., Vile R., et al. Reovirus activates human dendritic cells to promote innate antitumor immunity. J. Immunol. 2008;180:6018–6026. doi: 10.4049/jimmunol.180.9.6018.
    1. Comins C., Spicer J., Protheroe A., Roulstone V., Twigger K., White C.M., Vile R., Melcher A., Coffey M.C., Mettinger K.L., et al. REO-10: A phase I study of intravenous reovirus and docetaxel in patients with advanced cancer. Clin. Cancer Res. Off. J. Am. Assoc. Cancer Res. 2010;16:5564–5572. doi: 10.1158/1078-0432.CCR-10-1233.
    1. Galanis E., Markovic S.N., Suman V.J., Nuovo G.J., Vile R.G., Kottke T.J., Nevala W.K., Thompson M.A., Lewis J.E., Rumilla K.M., et al. Phase II trial of intravenous administration of Reolysin((R)) (Reovirus Serotype-3-dearing Strain) in patients with metastatic melanoma. Mol. Ther. J. Am. Soc. Gene Ther. 2012;20:1998–2003. doi: 10.1038/mt.2012.146.
    1. Rajani K., Parrish C., Kottke T., Thompson J., Zaidi S., Ilett L., Shim K.G., Diaz R.M., Pandha H., Harrington K., et al. Combination therapy with reovirus and anti-PD-1 blockade controls tumor growth through innate and adaptive immune responses. Mol. Ther. J. Am. Soc. Gene Ther. 2015 doi: 10.1038/mt.2015.156.
    1. Crouse J., Kalinke U., Oxenius A. Regulation of antiviral T cell responses by type I interferons. Nat. Rev. Immunol. 2015;15:231–242. doi: 10.1038/nri3806.
    1. Diamond M.S., Kinder M., Matsushita H., Mashayekhi M., Dunn G.P., Archambault J.M., Lee H., Arthur C.D., White J.M., Kalinke U., et al. Type I interferon is selectively required by dendritic cells for immune rejection of tumors. J. Exp. Med. 2011;208:1989–2003. doi: 10.1084/jem.20101158.
    1. Burnette B.C., Liang H., Lee Y., Chlewicki L., Khodarev N.N., Weichselbaum R.R., Fu Y.X., Auh S.L. The efficacy of radiotherapy relies upon induction of type i interferon-dependent innate and adaptive immunity. Cancer Res. 2011;71:2488–2496. doi: 10.1158/0008-5472.CAN-10-2820.
    1. Lim J.Y., Gerber S.A., Murphy S.P., Lord E.M. Type I interferons induced by radiation therapy mediate recruitment and effector function of CD8(+) T cells. Cancer Immunol. Immunother. CII. 2014;63:259–271. doi: 10.1007/s00262-013-1506-7.
    1. Schiavoni G., Sistigu A., Valentini M., Mattei F., Sestili P., Spadaro F., Sanchez M., Lorenzi S., D’Urso M.T., Belardelli F., et al. Cyclophosphamide synergizes with type I interferons through systemic dendritic cell reactivation and induction of immunogenic tumor apoptosis. Cancer Res. 2011;71:768–778. doi: 10.1158/0008-5472.CAN-10-2788.
    1. Woo S.R., Fuertes M.B., Corrales L., Spranger S., Furdyna M.J., Leung M.Y., Duggan R., Wang Y., Barber G.N., Fitzgerald K.A., et al. STING-dependent cytosolic DNA sensing mediates innate immune recognition of immunogenic tumors. Immunity. 2014;41:830–842. doi: 10.1016/j.immuni.2014.10.017.
    1. Ferrantini M., Capone I., Belardelli F. Interferon-alpha and cancer: Mechanisms of action and new perspectives of clinical use. Biochimie. 2007;89:884–893. doi: 10.1016/j.biochi.2007.04.006.
    1. Thompson M.R., Kaminski J.J., Kurt-Jones E.A., Fitzgerald K.A. Pattern recognition receptors and the innate immune response to viral infection. Viruses. 2011;3:920–940. doi: 10.3390/v3060920.
    1. Andtbacka R.H., Kaufman H.L., Collichio F., Amatruda T., Senzer N., Chesney J., Delman K.A., Spitler L.E., Puzanov I., Agarwala S.S., et al. Talimogene Laherparepvec Improves Durable Response Rate in Patients with Advanced Melanoma. J. Clin. Oncol. Off. J. Am. Soc. Clin. Oncol. 2015 doi: 10.1200/JCO.2014.58.3377.
    1. FDA . FDA News Release. FDA; Silver Spring, MD, USA: 2015. FDA approves first-of-its-kind product for the treatment of melanoma.
    1. Liu B.L., Robinson M., Han Z.Q., Branston R.H., English C., Reay P., McGrath Y., Thomas S.K., Thornton M., Bullock P., et al. ICP34.5 deleted herpes simplex virus with enhanced oncolytic, immune stimulating, and anti-tumour properties. Gene Ther. 2003;10:292–303. doi: 10.1038/sj.gt.3301885.
    1. Senzer N.N., Kaufman H.L., Amatruda T., Nemunaitis M., Reid T., Daniels G., Gonzalez R., Glaspy J., Whitman E., Harrington K., 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;27:5763–5771. doi: 10.1200/JCO.2009.24.3675.

Source: PubMed

Sponsorit ja yhteistyökumppanit

Sairaudet

Huumeiden interventiot

3
Tilaa