Oncolytic virotherapy relies on the administration of non-pathogenic viral strains that selectively infect and kill malignant cells while favoring the elicitation of a therapeutically relevant tumor-targeting immune response. During the past few years, great efforts have been dedicated to the development of oncolytic viruses with improved specificity and potency. Such an intense wave of investigation has culminated this year in the regulatory approval by the US Food and Drug Administration (FDA) of a genetically engineered oncolytic viral strain for use in melanoma patients. Here, we summarize recent preclinical and clinical advances in oncolytic virotherapy.

Group of Immune receptors of the Innate and Adaptive System Institut d'Investigacions Biomédiques August Pi i Sunyer Barcelona Spain

Gustave Roussy Cancer Campus Villejuif France

Gustave Roussy Cancer Campus Villejuif France; INSERM U1015 CICBT507 Villejuif France

INSERM U1138 Paris France; Université Paris Descartes Paris 5 Sorbonne Paris Cité Paris France; Université Pierre et Marie Curie Paris 6 Paris France; Equipe 11 labellisée par la Ligue Nationale contre le Cancer Center de Recherche des Cordeliers Paris France; Gustave Roussy Cancer Campus Villejuif France

INSERM U1138 Paris France; Université Paris Descartes Paris 5 Sorbonne Paris Cité Paris France; Université Pierre et Marie Curie Paris 6 Paris France; Equipe 11 labellisée par la Ligue Nationale contre le Cancer Center de Recherche des Cordeliers Paris France; Pôle de Biologie Hôpital Européen Georges Pompidou AP HP Paris France; Metabolomics and Cell Biology Platforms Gustave Roussy Cancer Campus Villejuif France; Department of Women's and Children's Health Karolinska University Hospital Stockholm Sweden

INSERM U1138 Paris France; Université Paris Descartes Paris 5 Sorbonne Paris Cité Paris France; Université Pierre et Marie Curie Paris 6 Paris France; Equipe 13 Center de Recherche des Cordeliers Paris France

INSERM U1138 Paris France; Université Paris Descartes Paris 5 Sorbonne Paris Cité Paris France; Université Pierre et Marie Curie Paris 6 Paris France; Laboratory of Integrative Cancer Immunology Centre de Recherche des Cordeliers Paris France

Sotio Prague Czech Republic; Dept of Immunology 2nd Faculty of Medicine and University Hospital Motol Charles University Prague Czech Republic

Transgene S A Illkirch Graffenstaden France

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Puzanov I, Milhem MM, Andtbacka RHI, Minor DR, Hamid O, Li A, Chou J, Kaufman H. Survival, safety, and response patterns in a phase 1b multicenter trial of talimogene laherparepvec (T-VEC) and ipilimumab (ipi) in previously untreated, unresected stage IIIB-IV melanoma. ASCO Meeting Abstracts 2015; 33:9063

Vidal L, Pandha HS, Yap TA, White CL, Twigger K, Vile RG, Melcher A, Coffey M, Harrington KJ, DeBono JS. A phase I study of intravenous oncolytic reovirus type 3 Dearing in patients with advanced cancer. Clin Cancer Res 2008; 14:7127-37; PMID:18981012; http://dx.doi.org/10.1158/1078-0432.CCR-08-0524 PubMed DOI

Kicielinski KP, Chiocca EA, Yu JS, Gill GM, Coffey M, Markert JM. Phase 1 clinical trial of intratumoral reovirus infusion for the treatment of recurrent malignant gliomas in adults. Mol Ther 2014; 22:1056-62; PMID:24553100; http://dx.doi.org/10.1038/mt.2014.21 PubMed DOI PMC

Sborov DW, Nuovo GJ, Stiff A, Mace T, Lesinski GB, Benson DM Jr., Efebera YA, Rosko AE, Pichiorri F, Grever MR et al.. A phase I trial of single-agent reolysin in patients with relapsed multiple myeloma. Clin Cancer Res 2014; 20:5946-55; PMID:25294913; http://dx.doi.org/10.1158/1078-0432.CCR-14-1404 PubMed DOI PMC

Weir GM, Hrytsenko O, Stanford MM, Berinstein NL, Karkada M, Liwski RS, Mansour M. Metronomic cyclophosphamide enhances HPV16E7 peptide vaccine induced antigen-specific and cytotoxic T-cell mediated antitumor immune response. Oncoimmunology 2014; 3:e953407; PMID:25960932; http://dx.doi.org/10.4161/21624011.2014.953407 PubMed DOI PMC

Sheng Sow H, Mattarollo SR. Combining low-dose or metronomic chemotherapy with anticancer vaccines: A therapeutic opportunity for lymphomas. Oncoimmunology 2013; 2:e27058; PMID:24498564; http://dx.doi.org/10.4161/onci.27058 PubMed DOI PMC

Kolb EA, Sampson V, Stabley D, Walter A, Sol-Church K, Cripe T, Hingorani P, Ahern CH, Weigel BJ, Zwiebel J et al.. 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 2015; 62:751-8; PMID:25728527; http://dx.doi.org/10.1002/pbc.25464 PubMed DOI PMC

Roulstone V, Khan K, Pandha HS, Rudman S, Coffey M, Gill GM, Melcher AA, Vile R, Harrington KJ, de Bono J et al.. Phase I trial of cyclophosphamide as an immune modulator for optimizing oncolytic reovirus delivery to solid tumors. Clin Cancer Res 2015; 21:1305-12; PMID:25424857; http://dx.doi.org/10.1158/1078-0432.CCR-14-1770 PubMed DOI PMC

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Andtbacka RH, Curti B, Hallmeyer S, Shafren DR. Phase II CALM study: Changes in the tumor microenvironment induced by the immunotherapeutic agent coxsackievirus A21 delivered intratumorally in patients with advanced melanoma. Cancer Res 2015; 75:Abstract CT214

Andtbacka RHI, Curti BD, Kaufman H, Daniels GA, Nemunaitis JJ, Spitler LE, Hallmeyer S, Lutzky J, Schultz SM, Whitman ED, Zhou K et al.. Final data from CALM: A phase II study of Coxsackievirus A21 (CVA21) oncolytic virus immunotherapy in patients with advanced melanoma. ASCO Meeting Abstracts 2015; 33:9030

Pandha H, Harrington K, Ralph C, Melcher A, Shafren DR. Intravenous delivery of a novel oncolytic immunotherapy agent, CAVATAK, in advanced cancer patients. Cancer Res 2015; 75:Abstract CT205; http://dx.doi.org/10.1158/1538-7445.AM2015-CT205 DOI

Bramante S, Koski A, Kipar A, Diaconu I, Liikanen I, Hemminki O, Vassilev L, Parviainen S, Cerullo V, Pesonen SK et al.. Serotype chimeric oncolytic adenovirus coding for GM-CSF for treatment of sarcoma in rodents and humans. Int J Cancer 2014; 135:720-30; PMID:24374597; http://dx.doi.org/10.1002/ijc.28696 PubMed DOI

Ranki T, Joensuu T, Jager E, Karbach J, Wahle C, Kairemo K, Alanko T, Partanen K, Turkki R, Linder N et al.. Local treatment of a pleural mesothelioma tumor with ONCOS-102 induces a systemic antitumor CD8 T-cell response, prominent infiltration of CD8 lymphocytes and Th1 type polarization. Oncoimmunology 2014; 3:e958937; PMID:25941579; http://dx.doi.org/10.4161/21624011.2014.958937 PubMed DOI PMC

Bramante S, Kaufmann JK, Veckman V, Liikanen I, Nettelbeck DM, Hemminki O, Vassilev L, Cerullo V, Oksanen M, Heiskanen R et al.. Treatment of melanoma with a serotype 5/3 chimeric oncolytic adenovirus coding for GM-CSF: Results in vitro, in rodents and in humans. Int J Cancer 2015; 137:1775-83; PMID:25821063; http://dx.doi.org/10.1002/ijc.29536 PubMed DOI

Kanerva A, Koski A, Liikanen I, Oksanen M, Joensuu T, Hemminki O, Palmgren J, Hemminki K, Hemminki A. Case-control estimation of the impact of oncolytic adenovirus on the survival of patients with refractory solid tumors. Mol Ther 2015; 23:321-9; PMID:25381801; http://dx.doi.org/10.1038/mt.2014.218 PubMed DOI PMC

Hemminki O, Parviainen S, Juhila J, Turkki R, Linder N, Lundin J, Kankainen M, Ristimäki A, Koski A, Liikanen I et al.. Immunological data from cancer patients treated with Ad5/3-E2F-Delta24-GMCSF suggests utility for tumor immunotherapy. Oncotarget 2015; 6:4467-81; PMID:25714011; http://dx.doi.org/10.18632/oncotarget.2901 PubMed DOI PMC

Pesonen SA, Ranki T, Jager E, Karbach J, Wahle C, Joensuu TK, Alanko T, Partanen K, Kairemo K, Turkki R et al.. An evaluation of local and systemic immune markers following intratumoral administration of a chimeric adenovirus Ad5/3-D24-GMCSF in refractory cancer patients with solid tumors. ASCO Meeting Abstracts 2015; 33:3085

Park BH, Hwang T, Liu TC, Sze DY, Kim JS, Kwon HC, Oh SY, Han SY, Yoon JH, Hong SH 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; PMID:18495536; http://dx.doi.org/10.1016/S1470-2045(08)70107-4 PubMed DOI

Park SH, Breitbach CJ, Lee J, Park JO, Lim HY, Kang WK, Moon A, Mun JH, Sommermann EM, Maruri Avidal L et al.. Phase 1b Trial of Biweekly Intravenous Pexa-Vec (JX-594), an Oncolytic and Immunotherapeutic Vaccinia Virus in Colorectal Cancer. Mol Ther 2015; 23:1532-40; PMID:26073886; http://dx.doi.org/10.1038/mt.2015.109 PubMed DOI PMC

Cripe TP, Ngo MC, Geller JI, Louis CU, Currier MA, Racadio JM, Towbin AJ, Rooney CM, Pelusio A, Moon A et al.. Phase 1 study of intratumoral Pexa-Vec (JX-594), an oncolytic and immunotherapeutic vaccinia virus, in pediatric cancer patients. Mol Ther 2015; 23:602-8; PMID:25531693; http://dx.doi.org/10.1038/mt.2014.243 PubMed DOI PMC

Wang H, Chen NG, Minev BR, Szalay AA. Oncolytic vaccinia virus GLV-1h68 strain shows enhanced replication in human breast cancer stem-like cells in comparison to breast cancer cells. J Transl Med 2012; 10:167; PMID:22901246; http://dx.doi.org/10.1186/1479-5876-10-167 PubMed DOI PMC

Krug LM, Zauderer MG, Adusumili PS, McGee E, Sepkowitz K, Klang M, Yu YA, Scigalla P, Rusch VW. Phase I study of intra-pleural administration of GL-ONC1, an oncolytic vaccinia virus, in patients with malignant pleural effusion. ASCO Meeting Abstracts 2015; 33:7559

Kono K, Mimura K. Immunogenic tumor cell death induced by chemoradiotherapy in a clinical setting. Oncoimmunology 2013; 2:e22197; PMID:23482346; http://dx.doi.org/10.4161/onci.22197 PubMed DOI PMC

Golden EB, Frances D, Pellicciotta I, Demaria S, Helen Barcellos-Hoff M, Formenti SC. Radiation fosters dose-dependent and chemotherapy-induced immunogenic cell death. Oncoimmunology 2014; 3:e28518; PMID:25071979; http://dx.doi.org/10.4161/onci.28518 PubMed DOI PMC

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Kooby DA, Carew JF, Halterman MW, Mack JE, Bertino JR, Blumgart LH, Federoff HJ, Fong Y. Oncolytic viral therapy for human colorectal cancer and liver metastases using a multi-mutated herpes simplex virus type-1 (G207). FASEB J 1999; 13:1325-34; PMID:10428757 PubMed

Markert JM, Razdan SN, Kuo HC, Cantor A, Knoll A, Karrasch M, Nabors LB, Markiewicz M, Agee BS, Coleman JM et al.. A phase 1 trial of oncolytic HSV-1, G207, given in combination with radiation for recurrent GBM demonstrates safety and radiographic responses. Mol Ther 2014; 22:1048-55; PMID:24572293; http://dx.doi.org/10.1038/mt.2014.22 PubMed DOI PMC

Morton CL, Houghton PJ, Kolb EA, Gorlick R, Reynolds CP, Kang MH, Maris JM, Keir ST, Wu J, Smith MA. Initial testing of the replication competent Seneca Valley virus (NTX-010) by the pediatric preclinical testing program. Pediatr Blood Cancer 2010; 55:295-303; PMID:20582972; http://dx.doi.org/10.1002/pbc.22535 PubMed DOI PMC

Burke MJ, Ahern C, Weigel BJ, Poirier JT, Rudin CM, Chen Y, Cripe TP, Bernhardt MB, Blaney SM. Phase I trial of Seneca Valley Virus (NTX-010) in children with relapsed/refractory solid tumors: a report of the Children's Oncology Group. Pediatr Blood Cancer 2015; 62:743-50; PMID:25307519; http://dx.doi.org/10.1002/pbc.25269 PubMed DOI PMC

Barton KN, Paielli D, Zhang Y, Koul S, Brown SL, Lu M, Seely J, Kim JH, Freytag SO. Second-generation replication-competent oncolytic adenovirus armed with improved suicide genes and ADP gene demonstrates greater efficacy without increased toxicity. Mol Ther 2006; 13:347-56; PMID:16290236; http://dx.doi.org/10.1016/j.ymthe.2005.10.005 PubMed DOI

Vacchelli E, Vitale I, Tartour E, Eggermont A, Sautes-Fridman C, Galon J, Zitvogel L, Kroemer G, Galluzzi L. Trial Watch: Anticancer radioimmunotherapy. Oncoimmunology 2013; 2:e25595; PMID:24319634; http://dx.doi.org/10.4161/onci.25595 PubMed DOI PMC

Bloy N, Pol J, Manic G, Vitale I, Eggermont A, Galon J, Tartour E, Zitvogel L, Kroemer G, Galluzzi L. Trial Watch: Radioimmunotherapy for oncological indications. Oncoimmunology 2014; 3:e954929; PMID:25941606; http://dx.doi.org/10.4161/21624011.2014.954929 PubMed DOI PMC

Freytag SO, Stricker H, Lu M, Elshaikh M, Aref I, Pradhan D, Levin K, Kim JH, Peabody J, Siddiqui F et al.. Prospective randomized phase 2 trial of intensity modulated radiation therapy with or without oncolytic adenovirus-mediated cytotoxic gene therapy in intermediate-risk prostate cancer. Int J Radiat Oncol Biol Phys 2014; 89:268-76; PMID:24837889; http://dx.doi.org/10.1016/j.ijrobp.2014.02.034 PubMed DOI PMC

Kimata H, Takakuwa H, Goshima F, Teshigahara O, Nakao A, Kurata T, Sata T, Nishiyama Y. Effective treatment of disseminated peritoneal colon cancer with new replication-competent herpes simplex viruses. Hepatogastroenterology 2003; 50:961-6; PMID:12845959 PubMed

Kasuya H, Kodera Y, Nakao A, Yamamura K, Gewen T, Zhiwen W, Hotta Y, Yamada S, Fujii T, Fukuda S et al.. Phase I dose-escalation clinical trial of HF10 oncolytic herpes virus in 17 Japanese patients with advanced cancer. Hepatogastroenterology 2014; 61:599-605; PMID:26176043 PubMed

Dingli D, Peng KW, Harvey ME, Greipp PR, O'Connor MK, Cattaneo R, Morris JC, Russell SJ. Image-guided radiovirotherapy for multiple myeloma using a recombinant measles virus expressing the thyroidal sodium iodide symporter. Blood 2004; 103:1641-6; PMID:14604966; http://dx.doi.org/10.1182/blood-2003-07-2233 PubMed DOI

Fonteneau JF, Guillerme JB, Tangy F, Gregoire M. Attenuated measles virus used as an oncolytic virus activates myeloid and plasmacytoid dendritic cells. Oncoimmunology 2013; 2:e24212; PMID:23762802; http://dx.doi.org/10.4161/onci.24212 PubMed DOI PMC

Russell SJ, Federspiel MJ, Peng KW, Tong C, Dingli D, Morice WG, Lowe V, O'Connor MK, Kyle RA, Leung N et al.. Remission of disseminated cancer after systemic oncolytic virotherapy. Mayo Clin Proc 2014; 89:926-33; PMID:24835528; http://dx.doi.org/10.1016/j.mayocp.2014.04.003 PubMed DOI PMC

Umeoka T, Kawashima T, Kagawa S, Teraishi F, Taki M, Nishizaki M, Kyo S, Nagai K, Urata Y, Tanaka N et al.. Visualization of intrathoracically disseminated solid tumors in mice with optical imaging by telomerase-specific amplification of a transferred green fluorescent protein gene. Cancer Res 2004; 64:6259-65; PMID:15342413; http://dx.doi.org/10.1158/0008-5472.CAN-04-1335 PubMed DOI

Tanabe S, Tazawa H, Kagawa S, Noma K, Takehara K, Koujima T, Kashima H, Kato T, Kuroda S, Kikuchi S et al.. Phase I/II trial of endoscopic intratumoral administration of OBP-301, a novel telomerase-specific oncolytic virus, with radiation in elderly esophageal cancer patients. Cancer Res 2015; 75:Abstract CT213; http://dx.doi.org/10.1158/1538-7445.AM2015-CT123 DOI

Thorne SH. Immunotherapeutic potential of oncolytic vaccinia virus. Front Oncol 2014; 4:155; PMID:24987615; http://dx.doi.org/10.3389/fonc.2014.00155 PubMed DOI PMC

Zeh HJ, Downs-Canner S, McCart JA, Guo ZS, Rao UN, Ramalingam L, Thorne SH, Jones HL, Kalinski P, Wieckowski E et al.. First-in-man study of western reserve strain oncolytic vaccinia virus: safety, systemic spread, and antitumor activity. Mol Ther 2015; 23:202-14; PMID:25292189; http://dx.doi.org/10.1038/mt.2014.194 PubMed DOI PMC

Spary LK, Salimu J, Webber JP, Clayton A, Mason MD, Tabi Z. Tumor stroma-derived factors skew monocyte to dendritic cell differentiation toward a suppressive CD14 PD-L1 phenotype in prostate cancer. Oncoimmunology 2014; 3:e955331; PMID:25941611; http://dx.doi.org/10.4161/21624011.2014.955331 PubMed DOI PMC

Mesange P, Poindessous V, Sabbah M, Escargueil AE, de Gramont A, Larsen AK. Intrinsic bevacizumab resistance is associated with prolonged activation of autocrine VEGF signaling and hypoxia tolerance in colorectal cancer cells and can be overcome by nintedanib, a small molecule angiokinase inhibitor. Oncotarget 2014; 5:4709-21; PMID:25015210; http://dx.doi.org/10.18632/oncotarget.1671 PubMed DOI PMC

Zitvogel L, Galluzzi L, Kepp O, Smyth MJ, Kroemer G. Type I interferons in anticancer immunity. Nat Rev Immunol 2015; 15:405-14; PMID:26027717; http://dx.doi.org/10.1038/nri3845 PubMed DOI

Arulanandam R, Batenchuk C, Angarita FA, Ottolino-Perry K, Cousineau S, Mottashed A, Burgess E, Falls TJ, De Silva N, Tsang J et al.. VEGF-Mediated Induction of PRD1-BF1/Blimp1 Expression Sensitizes Tumor Vasculature to Oncolytic Virus Infection. Cancer Cell 2015; 28:210-24; PMID:26212250; http://dx.doi.org/10.1016/j.ccell.2015.06.009 PubMed DOI

Kim BR, Yoon K, Byun HJ, Seo SH, Lee SH, Rho SB. The anti-tumor activator sMEK1 and paclitaxel additively decrease expression of HIF-1alpha and VEGF via mTORC1-S6K/4E-BP-dependent signaling pathways. Oncotarget 2014; 5:6540-51; PMID:25153728; http://dx.doi.org/10.18632/oncotarget.2119 PubMed DOI PMC

Lovat F, Ishii H, Schiappacassi M, Fassan M, Barbareschi M, Galligioni E, Gasparini P, Baldassarre G, Croce CM, Vecchione A. LZTS1 downregulation confers paclitaxel resistance and is associated with worse prognosis in breast cancer. Oncotarget 2014; 5:970-7; PMID:24448468; http://dx.doi.org/10.18632/oncotarget.1630 PubMed DOI PMC

Arulanandam R, Batenchuk C, Varette O, Zakaria C, Garcia V, Forbes NE, Davis C, Krishnan R, Karmacharya R, Cox J et al.. Microtubule disruption synergizes with oncolytic virotherapy by inhibiting interferon translation and potentiating bystander killing. Nat Commun 2015; 6:6410; PMID:25817275; http://dx.doi.org/10.1038/ncomms7410 PubMed DOI

Aranda F, Vacchelli E, Obrist F, Eggermont A, Galon J, Herve Fridman W, Cremer I, Tartour E, Zitvogel L, Kroemer G et al.. Trial Watch: Adoptive cell transfer for anticancer immunotherapy. Oncoimmunology 2014; 3:e28344; PMID:25050207; http://dx.doi.org/10.4161/onci.28344 PubMed DOI PMC

Vacchelli E, Eggermont A, Fridman WH, Galon J, Tartour E, Zitvogel L, Kroemer G, Galluzzi L. Trial Watch: Adoptive cell transfer for anticancer immunotherapy. Oncoimmunology 2013; 2:e24238; PMID:23762803; http://dx.doi.org/10.4161/onci.24238 PubMed DOI PMC

Nishio N, Diaconu I, Liu H, Cerullo V, Caruana I, Hoyos V, Bouchier-Hayes L, Savoldo B, Dotti G. Armed oncolytic virus enhances immune functions of chimeric antigen receptor-modified T cells in solid tumors. Cancer Res 2014; 74:5195-205; PMID:25060519; http://dx.doi.org/10.1158/0008-5472.CAN-14-0697 PubMed DOI PMC

Kroemer G, Galluzzi L, Kepp O, Zitvogel L. Immunogenic cell death in cancer therapy. Annu Rev Immunol 2013; 31:51-72; PMID:23157435; http://dx.doi.org/10.1146/annurev-immunol-032712-100008 PubMed DOI

Vacchelli E, Aranda F, Eggermont A, Galon J, Sautes-Fridman C, Cremer I, Zitvogel L, Kroemer G, Galluzzi L. Trial Watch: Chemotherapy with immunogenic cell death inducers. Oncoimmunology 2014; 3:e27878; PMID:24800173; http://dx.doi.org/10.4161/onci.27878 PubMed DOI PMC

Hamouda MA, Belhacene N, Puissant A, Colosetti P, Robert G, Jacquel A, Mari B, Auberger P, Luciano F. The small heat shock protein B8 (HSPB8) confers resistance to bortezomib by promoting autophagic removal of misfolded proteins in multiple myeloma cells. Oncotarget 2014; 5:6252-66; PMID:25051369; http://dx.doi.org/10.18632/oncotarget.2193 PubMed DOI PMC

Siveen KS, Mustafa N, Li F, Kannaiyan R, Ahn KS, Kumar AP, Chng WJ, Sethi G. Thymoquinone overcomes chemoresistance and enhances the anticancer effects of bortezomib through abrogation of NF-kappaB regulated gene products in multiple myeloma xenograft mouse model. Oncotarget 2014; 5:634-48; PMID:24504138; http://dx.doi.org/10.18632/oncotarget.1596 PubMed DOI PMC

Vacchelli E, Senovilla L, Eggermont A, Fridman WH, Galon J, Zitvogel L, Kroemer G, Galluzzi L. Trial watch: Chemotherapy with immunogenic cell death inducers. Oncoimmunology 2013; 2:e23510; PMID:23687621; http://dx.doi.org/10.4161/onci.23510 PubMed DOI PMC

Yoo JY, Hurwitz BS, Bolyard C, Yu JG, Zhang J, Selvendiran K, Rath KS, He S, Bailey Z, Eaves D et al.. Bortezomib-induced unfolded protein response increases oncolytic HSV-1 replication resulting in synergistic antitumor effects. Clin Cancer Res 2014; 20:3787-98; PMID:24815720; http://dx.doi.org/10.1158/1078-0432.CCR-14-0553 PubMed DOI PMC

Vacchelli E, Eggermont A, Galon J, Sautes-Fridman C, Zitvogel L, Kroemer G, Galluzzi L. Trial watch: Monoclonal antibodies in cancer therapy. Oncoimmunology 2013; 2:e22789; PMID:23482847; http://dx.doi.org/10.4161/onci.22789 PubMed DOI PMC

Vacchelli E, Aranda F, Eggermont A, Galon J, Sautes-Fridman C, Zitvogel L, Kroemer G, Galluzzi L. Trial Watch: Tumor-targeting monoclonal antibodies in cancer therapy. Oncoimmunology 2014; 3:e27048; PMID:24605265; http://dx.doi.org/10.4161/onci.27048 PubMed DOI PMC

Parrish C, Scott GB, Migneco G, Scott KJ, Steele LP, Ilett E, West EJ, Hall K, Selby PJ, Buchanan D et al.. Oncolytic reovirus enhances rituximab-mediated antibody-dependent cellular cytotoxicity against chronic lymphocytic leukaemia. Leukemia 2015; 29:1799-810; PMID:25814029; http://dx.doi.org/10.1038/leu.2015.88 PubMed DOI PMC

Ho SS, Gasser S. NKG2D ligands link oncogenic RAS to innate immunity. Oncoimmunology 2013; 2:e22244; PMID:23482418; http://dx.doi.org/10.4161/onci.22244 PubMed DOI PMC

Komatsu Y, Christian SL, Ho N, Pongnopparat T, Licursi M, Hirasawa K. Oncogenic Ras inhibits IRF1 to promote viral oncolysis. Oncogene 2015; 34:3985-93; PMID:25347735; http://dx.doi.org/10.1038/onc.2014.331 PubMed DOI

Ilkow CS, Marguerie M, Batenchuk C, Mayer J, Ben Neriah D, Cousineau S, Falls T, Jennings VA, Boileau M, Bellamy D et al.. Reciprocal cellular cross-talk within the tumor microenvironment promotes oncolytic virus activity. Nat Med 2015; 21:530-6; PMID:25894825; http://dx.doi.org/10.1038/nm.3848 PubMed DOI

Gayral M, Lulka H, Hanoun N, Biollay C, Selves J, Vignolle-Vidoni A, Berthommé H, Trempat P, Epstein AL, Buscail L et al.. Targeted oncolytic herpes simplex virus type 1 eradicates experimental pancreatic tumors. Hum Gene Ther 2015; 26:104-13; PMID:25423447; http://dx.doi.org/10.1089/hum.2014.072 PubMed DOI PMC

Byrne SN, Sarchio SN. AMD3100 protects from UV-induced skin cancer. Oncoimmunology 2014; 3:e27562; PMID:24744978; http://dx.doi.org/10.4161/onci.27562 PubMed DOI PMC

Waldron TJ, Quatromoni JG, Karakasheva TA, Singhal S, Rustgi AK. Myeloid derived suppressor cells: Targets for therapy. Oncoimmunology 2013; 2:e24117; PMID:23734336; http://dx.doi.org/10.4161/onci.24117 PubMed DOI PMC

Gil M, Komorowski MP, Seshadri M, Rokita H, McGray AJ, Opyrchal M, Odunsi KO, Kozbor D. CXCL12/CXCR4 blockade by oncolytic virotherapy inhibits ovarian cancer growth by decreasing immunosuppression and targeting cancer-initiating cells. J Immunol 2014; 193:5327-37; PMID:25320277; http://dx.doi.org/10.4049/jimmunol.1400201 PubMed DOI PMC

Martens A, Zelba H, Garbe C, Pawelec G, Weide B. Monocytic myeloid-derived suppressor cells in advanced melanoma patients: Indirect impact on prognosis through inhibition of tumor-specific T-cell responses? Oncoimmunology 2014; 3:e27845; PMID:24800171; http://dx.doi.org/10.4161/onci.27845 PubMed DOI PMC

Clements DR, Sterea AM, Kim Y, Helson E, Dean CA, Nunokawa A, Coyle KM, Sharif T, Marcato P, Gujar SA et al.. Newly recruited CD11b+, GR-1+, Ly6C(high) myeloid cells augment tumor-associated immunosuppression immediately following the therapeutic administration of oncolytic reovirus. J Immunol 2015; 194:4397-412; PMID:25825443; http://dx.doi.org/10.4049/jimmunol.1402132 PubMed DOI

Paglino JC, Andres W, van den Pol AN. Autonomous parvoviruses neither stimulate nor are inhibited by the type I interferon response in human normal or cancer cells. J Virol 2014; 88:4932-42; PMID:24554651; http://dx.doi.org/10.1128/JVI.03508-13 PubMed DOI PMC

Zloza A, Kim DW, Kim-Schulze S, Jagoda MC, Monsurro V, Marincola FM, Kaufman HL. Immunoglobulin-like transcript 2 (ILT2) is a biomarker of therapeutic response to oncolytic immunotherapy with vaccinia viruses. J Immunother Cancer 2014; 2:1; PMID:24829758; http://dx.doi.org/10.1186/2051-1426-2-1 PubMed DOI PMC

Adkins I, Fucikova J, Garg AD, Agostinis P, Spisek R. Physical modalities inducing immunogenic tumor cell death for cancer immunotherapy. Oncoimmunology 2014; 3:e968434; PMID:25964865; http://dx.doi.org/10.4161/21624011.2014.968434 PubMed DOI PMC

Aranda F, Vacchelli E, Obrist F, Eggermont A, Galon J, Sautes-Fridman C, Cremer I, Henrik Ter Meulen J, Zitvogel L, Kroemer G et al.. Trial Watch: Toll-like receptor agonists in oncological indications. Oncoimmunology 2014; 3:e29179; PMID:25083332; http://dx.doi.org/10.4161/onci.29179 PubMed DOI PMC

Brenner C, Galluzzi L, Kepp O, Kroemer G. Decoding cell death signals in liver inflammation. J Hepatol 2013; 59:583-94; PMID:23567086; http://dx.doi.org/10.1016/j.jhep.2013.03.033 PubMed DOI

Vacchelli E, Eggermont A, Sautes-Fridman C, Galon J, Zitvogel L, Kroemer G, Galluzzi L. Trial Watch: Toll-like receptor agonists for cancer therapy. Oncoimmunology 2013; 2:e25238; PMID:24083080; http://dx.doi.org/10.4161/onci.25238 PubMed DOI PMC

Liikanen I, Koski A, Merisalo-Soikkeli M, Hemminki O, Oksanen M, Kairemo K, Joensuu T, Kanerva A, Hemminki A. Serum HMGB1 is a predictive and prognostic biomarker for oncolytic immunotherapy. Oncoimmunology 2015; 4:e989771; PMID:25949903; http://dx.doi.org/10.4161/2162402X.2014.989771 PubMed DOI PMC

Kuruppu D, Brownell AL, Shah K, Mahmood U, Tanabe KK. Molecular imaging with bioluminescence and PET reveals viral oncolysis kinetics and tumor viability. Cancer Res 2014; 74:4111-21; PMID:24876106; http://dx.doi.org/10.1158/0008-5472.CAN-13-3472 PubMed DOI PMC

Crouse J, Kalinke U, Oxenius A. Regulation of antiviral T cell responses by type I interferons. Nat Rev Immunol 2015; 15:231-42; PMID:25790790; http://dx.doi.org/10.1038/nri3806 PubMed DOI

McNab F, Mayer-Barber K, Sher A, Wack A, O'Garra A. Type I interferons in infectious disease. Nat Rev Immunol 2015; 15:87-103; PMID:25614319; http://dx.doi.org/10.1038/nri3787 PubMed DOI PMC

Sistigu A, Yamazaki T, Vacchelli E, Chaba K, Enot DP, Adam J, Vitale I, Goubar A, Baracco EE, Remédios C et al.. Cancer cell-autonomous contribution of type I interferon signaling to the efficacy of chemotherapy. Nat Med 2014; 20:1301-9; PMID:25344738; http://dx.doi.org/10.1038/nm.3708 PubMed DOI

Pol J, Bloy N, Obrist F, Eggermont A, Galon J, Cremer I, Erbs P, Limacher JM, Preville X, Zitvogel L et al.. Trial Watch: Oncolytic viruses for cancer therapy. Oncoimmunology 2014; 3:e28694; PMID:25097804; http://dx.doi.org/10.4161/onci.28694 PubMed DOI PMC

Ramesh N, Ge Y, Ennist DL, Zhu M, Mina M, Ganesh S, Reddy PS, Yu DC. CG0070, a conditionally replicating granulocyte macrophage colony-stimulating factor–armed oncolytic adenovirus for the treatment of bladder cancer. Clin Cancer Res 2006; 12:305-13; PMID:16397056; http://dx.doi.org/10.1158/1078-0432.CCR-05-1059 PubMed DOI

Huang TT, Hlavaty J, Ostertag D, Espinoza FL, Martin B, Petznek H, Rodriguez-Aguirre M, Ibañez CE, Kasahara N, Gunzburg W et al.. Toca 511 gene transfer and 5-fluorocytosine in combination with temozolomide demonstrates synergistic therapeutic efficacy in a temozolomide-sensitive glioblastoma model. Cancer Gene Ther 2013; 20:544-51; PMID:23969884; http://dx.doi.org/10.1038/cgt.2013.51 PubMed DOI

Perez OD, Logg CR, Hiraoka K, Diago O, Burnett R, Inagaki A, Jolson D, Amundson K, Buckley T, Lohse D et al.. Design and selection of Toca 511 for clinical use: modified retroviral replicating vector with improved stability and gene expression. Mol Ther 2012; 20:1689-98; PMID:22547150; http://dx.doi.org/10.1038/mt.2012.83 PubMed DOI PMC

Ostertag D, Amundson KK, Lopez Espinoza F, Martin B, Buckley T, Galvao da Silva AP, Lin AH, Valenta DT, Perez OD, Ibañez CE et al.. Brain tumor eradication and prolonged survival from intratumoral conversion of 5-fluorocytosine to 5-fluorouracil using a nonlytic retroviral replicating vector. Neuro Oncol 2012; 14:145-59; PMID:22070930; http://dx.doi.org/10.1093/neuonc/nor199 PubMed DOI PMC

Ghiringhelli F, Bruchard M, Apetoh L. Immune effects of 5-fluorouracil: Ambivalence matters. Oncoimmunology 2013; 2:e23139; PMID:23802066; http://dx.doi.org/10.4161/onci.23139 PubMed DOI PMC

Alonso MM, Gomez-Manzano C, Bekele BN, Yung WK, Fueyo J. Adenovirus-based strategies overcome temozolomide resistance by silencing the O6-methylguanine-DNA methyltransferase promoter. Cancer Res 2007; 67:11499-504; PMID:18089777; http://dx.doi.org/10.1158/0008-5472.CAN-07-5312 PubMed DOI

Alonso MM, Jiang H, Yokoyama T, Xu J, Bekele NB, Lang FF, Kondo S, Gomez-Manzano C, Fueyo J. Delta-24-RGD in combination with RAD001 induces enhanced anti-glioma effect via autophagic cell death. Mol Ther 2008; 16:487-93; PMID:18253154; http://dx.doi.org/10.1038/sj.mt.6300400 PubMed DOI

Kleijn A, Kloezeman J, Treffers-Westerlaken E, Fulci G, Leenstra S, Dirven C, Debets R, Lamfers M. The therapeutic efficacy of the oncolytic virus Delta24-RGD in a murine glioma model depends primarily on antitumor immunity. Oncoimmunology 2014; 3:e955697; PMID:25941622; http://dx.doi.org/10.4161/21624011.2014.955697 PubMed DOI PMC

Brichard VG, Godechal Q. MAGE-A3-specific anticancer immunotherapy in the clinical practice. Oncoimmunology 2013; 2:e25995; PMID:24244898; http://dx.doi.org/10.4161/onci.25995 PubMed DOI PMC

Schmidt N, Flecken T, Thimme R. Tumor-associated antigen specific CD8 T cells in hepatocellular carcinoma - a promising target for immunotherapy. Oncoimmunology 2014; 3:e954919; PMID:25941604; http://dx.doi.org/10.4161/21624011.2014.954919 PubMed DOI PMC

Vacchelli E, Eggermont A, Fridman WH, Galon J, Zitvogel L, Kroemer G, Galluzzi L. Trial Watch: Immunostimulatory cytokines. Oncoimmunology 2013; 2:e24850; PMID:24073369; http://dx.doi.org/10.4161/onci.24850 PubMed DOI PMC

Vacchelli E, Aranda F, Obrist F, Eggermont A, Galon J, Cremer I, Zitvogel L, Kroemer G, Galluzzi L. Trial watch: Immunostimulatory cytokines in cancer therapy. Oncoimmunology 2014; 3:e29030; PMID:25083328; http://dx.doi.org/10.4161/onci.29030 PubMed DOI PMC

Andtbacka RHI, Chastain M, Li A, Shilkrut M, Ross MI. Phase 2, multicenter, randomized, open-label trial assessing efficacy and safety of talimogene laherparepvec (T-VEC) neoadjuvant treatment (tx) plus surgery vs surgery for resectable stage IIIB/C and IVM1a melanoma (MEL). ASCO Meeting Abstracts 2015; 33:TPS9094

Taube JM. Unleashing the immune system: PD-1 and PD-Ls in the pre-treatment tumor microenvironment and correlation with response to PD-1/PD-L1 blockade. Oncoimmunology 2014; 3:e963413; PMID:25914862; http://dx.doi.org/10.4161/21624011.2014.963413 PubMed DOI PMC

Munir S, Andersen GH, Svane IM, Andersen MH. The immune checkpoint regulator PD-L1 is a specific target for naturally occurring CD4 T cells. Oncoimmunology 2013; 2:e23991; PMID:23734334; http://dx.doi.org/10.4161/onci.23991 PubMed DOI PMC

Kharaziha P, De Raeve H, Fristedt C, Li Q, Gruber A, Johnsson P, Kokaraki G, Panzar M, Laane E, Osterborg A et al.. Sorafenib has potent antitumor activity against multiple myeloma in vitro, ex vivo, and in vivo in the 5T33MM mouse model. Cancer Res 2012; 72:5348-62; PMID:22952216; http://dx.doi.org/10.1158/0008-5472.CAN-12-0658 PubMed DOI

Kharaziha P, Rodriguez P, Li Q, Rundqvist H, Bjorklund AC, Augsten M, Ullén A, Egevad L, Wiklund P, Nilsson S et al.. Targeting of distinct signaling cascades and cancer-associated fibroblasts define the efficacy of Sorafenib against prostate cancer cells. Cell Death Dis 2012; 3:e262; PMID:22278289; http://dx.doi.org/10.1038/cddis.2012.1 PubMed DOI PMC

Breitbach CJ, Moon A, Burke J, Hwang TH, Kirn DH. A phase 2, open-label, randomized study of pexa-vec (JX-594) administered by intratumoral injection in patients with unresectable primary hepatocellular Carcinoma. Methods Mol Biol 2015; 1317:343-57; PMID:26072416; http://dx.doi.org/10.1007/978-1-4939-2727-2_19 PubMed DOI

Vacchelli E, Eggermont A, Sautes-Fridman C, Galon J, Zitvogel L, Kroemer G, Galluzzi L. Trial watch: Oncolytic viruses for cancer therapy. Oncoimmunology 2013; 2:e24612; PMID:23894720; http://dx.doi.org/10.4161/onci.24612 PubMed DOI PMC

McNeish IA, Michael A, Twelves C, Glasspool R, Ajaz MA, Morrison R, Xeniou Q, Brown R, Fisher K, Blanc C. A phase I/II study of Enadenotucirev, an oncolytic Ad11/Ad3 chimeric group B adenovirus, administered intraperitoneally (IP): Dose finding and proof of concept in platinum-resistant epithelial ovarian cancer. ASCO Meeting Abstracts 2015; 33:TPS5611

Ferris RL, Gross ND, Nemunaitis JJ, Andtbacka RHI, Argiris A, Ohr J, Vetto JT, Senzer NN, Bedell C, Ungerleider RS et al.. Phase I trial of intratumoral therapy using HF10, an oncolytic HSV-1, demonstrates safety in HSV+/HSV- patients with refractory and superficial cancers. ASCO Meeting Abstracts 2014; 32:6082

Vonderheide RH, Burg JM, Mick R, Trosko JA, Li D, Shaik MN, Tolcher AW, Hamid O. Phase I study of the CD40 agonist antibody CP-870,893 combined with carboplatin and paclitaxel in patients with advanced solid tumors. Oncoimmunology 2013; 2:e23033; PMID:23483678; http://dx.doi.org/10.4161/onci.23033 PubMed DOI PMC

Galluzzi L, Senovilla L, Vitale I, Michels J, Martins I, Kepp O, Castedo M, Kroemer G. Molecular mechanisms of cisplatin resistance. Oncogene 2012; 31:1869-83; PMID:21892204; http://dx.doi.org/10.1038/onc.2011.384 PubMed DOI

Gujar SA, Clements D, Lee PW. Two is better than one: Complementing oncolytic virotherapy with gemcitabine to potentiate antitumor immune responses. Oncoimmunology 2014; 3:e27622; PMID:24804161; http://dx.doi.org/10.4161/onci.27622 PubMed DOI PMC

Multi-Institutional Evaluation of Pathologists' Assessment Compared to Immunoscore

Calreticulin and cancer

Trial Watch: Oncolytic viro-immunotherapy of hematologic and solid tumors

Trial watch: Immune checkpoint blockers for cancer therapy