Oncolytic Virotherapy for Cancer: Clinical Experience
Abstract
:1. Introduction
2. Herpes Simplex Virus-1
2.1. T-VEC
2.2. G207
2.3. G47Δ
2.4. ONCR-177
2.5. RP1/2
3. Vaccinia Virus
3.1. Pexa-Vec
3.2. GL-ONC1
3.3. vvDD
4. Adenovirus
4.1. DNX-2401
4.2. Enadenotucirev
4.3. LOAd703
4.4. ONCOS-102
4.5. RNA Viruses
5. Reovirus
5.1. Reolysin as Monotherapy
5.2. Reolysin in Combination with Other Therapies
6. Conclusions and Perspectives
Funding
Acknowledgments
Conflicts of Interest
References
- Mahoney, D.J.; Stojdl, D.F.; Laird, G. Virus therapy for cancer. Sci. Am. 2014, 311, 54–59. [Google Scholar] [CrossRef]
- Fukuhara, H.; Ino, Y.; Todo, T. Oncolytic virus therapy: A new era of cancer treatment at dawn. Cancer Sci. 2016, 107, 1373–1379. [Google Scholar] [CrossRef]
- Vaha-Koskela, M.J.; Heikkila, J.E.; Hinkkanen, A.E. Oncolytic viruses in cancer therapy. Cancer Lett. 2007, 254, 178–216. [Google Scholar] [CrossRef]
- Roizman, B. The function of herpes simplex virus genes: A primer for genetic engineering of novel vectors. Proc. Natl. Acad. Sci. USA 1996, 93, 11307–11312. [Google Scholar] [CrossRef] [Green Version]
- Koch, M.S.; Lawler, S.E.; Chiocca, E.A. HSV-1 Oncolytic Viruses from Bench to Bedside: An Overview of Current Clinical Trials. Cancers 2020, 12, 3514. [Google Scholar] [CrossRef]
- Rehman, H.; Silk, A.W.; Kane, M.P.; Kaufman, H.L. Into the clinic: Talimogene laherparepvec (T-VEC), a first-in-class intratumoral oncolytic viral therapy. J. Immunother. Cancer 2016, 4, 53. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kohlhapp, F.J.; Kaufman, H.L. Molecular Pathways: Mechanism of Action for Talimogene Laherparepvec, a New Oncolytic Virus Immunotherapy. Clin. Cancer Res. 2016, 22, 1048–1054. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Toda, M.; Martuza, R.L.; Rabkin, S.D. Tumor growth inhibition by intratumoral inoculation of defective herpes simplex virus vectors expressing granulocyte-macrophage colony-stimulating factor. Mol. Ther. 2000, 2, 324–329. [Google Scholar] [CrossRef] [PubMed]
- 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. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Hu, J.C.; Coffin, R.S.; Davis, C.J.; Graham, N.J.; Groves, N.; Guest, P.J.; Harrington, K.J.; James, N.D.; Love, C.A.; McNeish, I.; et al. A phase I study of OncoVEXGM-CSF, a second-generation oncolytic herpes simplex virus expressing granulocyte macrophage colony-stimulating factor. Clin. Cancer Res. 2006, 12, 6737–6747. [Google Scholar] [CrossRef] [Green Version]
- 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. [Google Scholar] [CrossRef]
- Harrington, K.J.; Andtbacka, R.H.; Collichio, F.; Downey, G.; Chen, L.; Szabo, Z.; Kaufman, H.L. Efficacy and safety of talimogene laherparepvec versus granulocyte-macrophage colony-stimulating factor in patients with stage IIIB/C and IVM1a melanoma: Subanalysis of the Phase III OPTiM trial. Onco Targets Ther. 2016, 9, 7081–7093. [Google Scholar] [CrossRef] [Green Version]
- Andtbacka, R.H.I.; Collichio, F.; Harrington, K.J.; Middleton, M.R.; Downey, G. hrling, K.; Kaufman, HL Final analyses of OPTiM: A randomized phase III trial of talimogene laherparepvec versus granulocyte-macrophage colony-stimulating factor in unresectable stage III-IV melanoma. J. Immunother. Cancer 2019, 7, 145. [Google Scholar] [CrossRef] [Green Version]
- Puzanov, I.; Milhem, M.M.; Minor, D.; Hamid, O.; Li, A.; Chen, L.; Chastain, M.; Gorski, K.S.; Anderson, A.; Chou, J.; et al. Talimogene Laherparepvec in Combination With Ipilimumab in Previously Untreated, Unresectable Stage IIIB-IV Melanoma. J. Clin. Oncol. 2016, 34, 2619–2626. [Google Scholar] [CrossRef] [Green Version]
- Ribas, A.; Dummer, R.; Puzanov, I.; VanderWalde, A.; Andtbacka, R.H.I.; Michielin, O.; Olszanski, A.J.; Malvehy, J.; Cebon, J.; Fernandez, E.; et al. Oncolytic Virotherapy Promotes Intratumoral T Cell Infiltration and Improves Anti-PD-1 Immunotherapy. Cell 2017, 170, 1109–1119.e10. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Cinatl, J., Jr.; Michaelis, M.; Driever, P.H.; Cinatl, J.; Hrabeta, J.; Suhan, T.; Doerr, H.W.; Vogel, J.U. Multimutated herpes simplex virus g207 is a potent inhibitor of angiogenesis. Neoplasia 2004, 6, 725–735. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Toda, M.; Rabkin, S.D.; Martuza, R.L. Treatment of human breast cancer in a brain metastatic model by G207, a replication-competent multimutated herpes simplex virus 1. Hum. Gene Ther. 1998, 9, 2177–2185. [Google Scholar] [CrossRef] [PubMed]
- Walker, J.R.; McGeagh, K.G.; Sundaresan, P.; Jorgensen, T.J.; Rabkin, S.D.; Martuza, R.L. Local and systemic therapy of human prostate adenocarcinoma with the conditionally replicating herpes simplex virus vector G207. Hum. Gene Ther. 1999, 10, 2237–2243. [Google Scholar] [CrossRef] [PubMed]
- Kooby, D.A.; Carew, J.F.; Halterman, M.W.; Mack, J.E.; Bertino, J.R.; Blumgart, L.H.; Federoff, H.J.; 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, 1325–1334. [Google Scholar] [CrossRef]
- Coukos, G.; Makrigiannakis, A.; Montas, S.; Kaiser, L.R.; Toyozumi, T.; Benjamin, I.; Albelda, S.M.; Rubin, S.C.; Molnar-Kimber, K.L. Multi-attenuated herpes simplex virus-1 mutant G207 exerts cytotoxicity against epithelial ovarian cancer but not normal mesothelium and is suitable for intraperitoneal oncolytic therapy. Cancer Gene Ther. 2000, 7, 275–283. [Google Scholar] [CrossRef] [Green Version]
- Chahlavi, A.; Todo, T.; Martuza, R.L.; Rabkin, S.D. Replication-competent herpes simplex virus vector G207 and cisplatin combination therapy for head and neck squamous cell carcinoma. Neoplasia 1999, 1, 162–169. [Google Scholar] [CrossRef] [Green Version]
- Todo, T.; Martuza, R.L.; Rabkin, S.D.; Johnson, P.A. Oncolytic herpes simplex virus vector with enhanced MHC class I presentation and tumor cell killing. Proc. Natl. Acad. Sci. USA 2001, 98, 6396–6401. [Google Scholar] [CrossRef] [Green Version]
- Markert, J.M.; Medlock, M.D.; Rabkin, S.D.; Gillespie, G.Y.; Todo, T.; Hunter, W.D.; Palmer, C.A.; Feigenbaum, F.; Tornatore, C.; Tufaro, F.; et al. Conditionally replicating herpes simplex virus mutant, G207 for the treatment of malignant glioma: Results of a phase I trial. Gene Ther. 2000, 7, 867–874. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Markert, J.M.; Razdan, S.N.; Kuo, H.C.; Cantor, A.; Knoll, A.; Karrasch, M.; Nabors, L.B.; Markiewicz, M.; Agee, B.S.; Coleman, J.M.; 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, 1048–1055. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Todo, T. Results of Phase II Clinical Trial of Oncolytic Herpes Virus G47Δ in patients with Glioblastoma. Neuro-Oncology 2019, 21 (Suppl. 6), vi4. [Google Scholar] [CrossRef]
- Edward, M.; Kennedy, T.F.; Behera, P.; Colthart, A.; Goshert, C.; Jacques, J.; Grant, K.; Grzesik, P.; Lerr, J.; Salta, L.V.; et al. Design of ONCR-177 base vector, a next generation oncolytic herpes simplex virus type-1, optimized for robust oncolysis, transgene expression and tumor-selective replication [abstract]. Cancer Res. 2019, 79 (Suppl. 13), 1455. [Google Scholar]
- Kennedy, E.M.; Farkaly, T.; Grzesik, P.; Lee, J.; Denslow, A.; Hewett, J.; Bryant, J.; Behara, P.; Goshert, C.; Wambua, D.; et al. Design of an Interferon-Resistant Oncolytic HSV-1 Incorporating Redundant Safety Modalities for Improved Tolerability. Mol. Ther. Oncolytics 2020, 18, 476–490. [Google Scholar] [CrossRef]
- Moss, B. Poxvirus DNA replication. Cold Spring Harb. Perspect. Biol. 2013, 5. [Google Scholar] [CrossRef] [Green Version]
- 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. 2006, 14, 361–370. [Google Scholar] [CrossRef] [PubMed]
- Mastrangelo, M.J.; Maguire, H.C., Jr.; Eisenlohr, L.C.; Laughlin, C.E.; Monken, C.E.; McCue, P.A.; Kovatich, A.J.; Lattime, E.C. Intratumoral recombinant GM-CSF-encoding virus as gene therapy in patients with cutaneous melanoma. Cancer Gene Ther. 1999, 6, 409–422. [Google Scholar] [CrossRef] [Green Version]
- 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. [Google Scholar] [CrossRef]
- Liu, T.C.; Hwang, T.; Park, B.H.; Bell, J.; Kirn, D.H. The targeted oncolytic poxvirus JX-594 demonstrates antitumoral, antivascular, and anti-HBV activities in patients with hepatocellular carcinoma. Mol. Ther. 2008, 16, 1637–1642. [Google Scholar] [CrossRef] [PubMed]
- Heo, J.; Breitbach, C.J.; Moon, A.; Kim, C.W.; Patt, R.; Kim, M.K.; Lee, Y.K.; Oh, S.Y.; Woo, H.Y.; Parato, K.; et al. Sequential therapy with JX-594, a targeted oncolytic poxvirus, followed by sorafenib in hepatocellular carcinoma: Preclinical and clinical demonstration of combination efficacy. Mol. Ther. 2011, 19, 1170–1179. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Breitbach, C.J.; Burke, J.; Jonker, D.; Stephenson, J.; Haas, A.R.; Chow, L.Q.; Nieva, J.; Hwang, T.H.; Moon, A.; Patt, R.; et al. Intravenous delivery of a multi-mechanistic cancer-targeted oncolytic poxvirus in humans. Nature 2011, 477, 99–102. [Google Scholar] [CrossRef]
- 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. [Google Scholar] [CrossRef] [PubMed]
- Moehler, M.; Heo, J.; Lee, H.C.; Tak, W.Y.; Chao, Y.; Paik, S.W.; Yim, H.J.; Byun, K.S.; Baron, A.; Ungerechts, G.; et al. Vaccinia-based oncolytic immunotherapy Pexastimogene Devacirepvec in patients with advanced hepatocellular carcinoma after sorafenib failure: A randomized multicenter Phase IIb trial (TRAVERSE). Oncoimmunology 2019, 8, 1615817. [Google Scholar] [CrossRef] [Green Version]
- Kelly, K.J.; Woo, Y.; Brader, P.; Yu, Z.; Riedl, C.; Lin, S.F.; Chen, N.; Yu, Y.A.; Rusch, V.W.; Szalay, A.A.; et al. Novel oncolytic agent GLV-1h68 is effective against malignant pleural mesothelioma. Hum. Gene Ther. 2008, 19, 774–782. [Google Scholar] [CrossRef]
- Ehrig, K.; Kilinc, M.O.; Chen, N.G.; Stritzker, J.; Buckel, L.; Zhang, Q.; Szalay, A.A. Growth inhibition of different human colorectal cancer xenografts after a single intravenous injection of oncolytic vaccinia virus GLV-1h68. J. Transl. Med. 2013, 11, 79. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Gholami, S.; Chen, C.H.; Belin, L.J.; Lou, E.; Fujisawa, S.; Antonacci, C.; Carew, A.; Chen, N.G.; De Brot, M.; Zanzonico, P.B.; et al. Vaccinia virus GLV-1h153 is a novel agent for detection and effective local control of positive surgical margins for breast cancer. Breast Cancer Res. 2013, 15, R26. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Haddad, D.; Zanzonico, P.B.; Carlin, S.; Chen, C.H.; Chen, N.G.; Zhang, Q.; Yu, Y.A.; Longo, V.; Mojica, K.; Aguilar, R.J.; et al. A vaccinia virus encoding the human sodium iodide symporter facilitates long-term image monitoring of virotherapy and targeted radiotherapy of pancreatic cancer. J. Nucl. Med. 2012, 53, 1933–1942. [Google Scholar] [CrossRef] [Green Version]
- Donat, U.; Weibel, S.; Hess, M.; Stritzker, J.; Hartl, B.; Sturm, J.B.; Chen, N.G.; Gentschev, I.; Szalay, A.A. Preferential colonization of metastases by oncolytic vaccinia virus strain GLV-1h68 in a human PC-3 prostate cancer model in nude mice. PLoS ONE 2012, 7, e45942. [Google Scholar] [CrossRef] [Green Version]
- Wang, H.; Chen, N.G.; Minev, B.R.; Szalay, A.A. 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. [Google Scholar] [CrossRef] [Green Version]
- Zeh, H.J.; Downs-Canner, S.; McCart, J.A.; Guo, Z.S.; Rao, U.N.; Ramalingam, L.; Thorne, S.H.; Jones, H.L.; 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, 202–214. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Thorne, S.H.; Hwang, T.H.; O’Gorman, W.E.; Bartlett, D.L.; Sei, S.; Kanji, F.; Brown, C.; Werier, J.; Cho, J.H.; Lee, D.E.; et al. Rational strain selection and engineering creates a broad-spectrum, systemically effective oncolytic poxvirus, JX-963. J. Clin. Investig. 2007, 117, 3350–3358. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Parato, K.A.; Breitbach, C.J.; Le Boeuf, F.; Wang, J.; Storbeck, C.; Ilkow, C.; Diallo, J.S.; Falls, T.; Burns, J.; Garcia, V.; et al. The oncolytic poxvirus JX-594 selectively replicates in and destroys cancer cells driven by genetic pathways commonly activated in cancers. Mol. Ther. 2012, 20, 749–758. [Google Scholar] [CrossRef] [Green Version]
- Downs-Canner, S.; Guo, Z.S.; Ravindranathan, R.; Breitbach, C.J.; O’Malley, M.E.; Jones, H.L.; Moon, A.; McCart, J.A.; Shuai, Y.; Zeh, H.J.; et al. Phase 1 Study of Intravenous Oncolytic Poxvirus (vvDD) in Patients with Advanced Solid Cancers. Mol. Ther. 2016, 24, 1492–1501. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- McConnell, M.J.; Imperiale, M.J. Biology of adenovirus and its use as a vector for gene therapy. Hum. Gene Ther. 2004, 15, 1022–1033. [Google Scholar] [CrossRef] [PubMed]
- Garber, K. China approves world’s first oncolytic virus therapy for cancer treatment. J. Natl. Cancer Inst. 2006, 98, 298–300. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Fueyo, J.; Alemany, R.; Gomez-Manzano, C.; Fuller, G.N.; Khan, A.; Conrad, C.A.; Liu, T.J.; Jiang, H.; Lemoine, M.G.; Suzuki, K.; et al. Preclinical characterization of the antiglioma activity of a tropism-enhanced adenovirus targeted to the retinoblastoma pathway. J. Natl. Cancer Inst. 2003, 95, 652–660. [Google Scholar] [CrossRef] [Green Version]
- Fueyo, J.; Gomez-Manzano, C.; Alemany, R.; Lee, P.S.; McDonnell, T.J.; Mitlianga, P.; Shi, Y.X.; Levin, V.A.; Yung, W.K.; Kyritsis, A.P. A mutant oncolytic adenovirus targeting the Rb pathway produces anti-glioma effect in vivo. Oncogene 2000, 19, 2–12. [Google Scholar] [CrossRef] [Green Version]
- Philbrick, B.; Adamson, D.C. DNX-2401: An investigational drug for the treatment of recurrent glioblastoma. Expert Opin. Investig. Drugs 2019, 28, 1041–1049. [Google Scholar] [CrossRef] [PubMed]
- Kuhn, I.; Harden, P.; Bauzon, M.; Chartier, C.; Nye, J.; Thorne, S.; Reid, T.; Ni, S.; Lieber, A.; Fisher, K.; et al. Directed evolution generates a novel oncolytic virus for the treatment of colon cancer. PLoS ONE 2008, 3, e2409. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Machiels, J.P.; Salazar, R.; Rottey, S.; Duran, I.; Dirix, L.; Geboes, K.; Wilkinson-Blanc, C.; Pover, G.; Alvis, S.; Champion, B.; et al. A phase 1 dose escalation study of the oncolytic adenovirus enadenotucirev, administered intravenously to patients with epithelial solid tumors (EVOLVE). J. Immunother. Cancer 2019, 7, 20. [Google Scholar] [CrossRef] [PubMed]
- Eriksson, E.; Milenova, I.; Wenthe, J.; Stahle, M.; Leja-Jarblad, J.; Ullenhag, G.; Dimberg, A.; Moreno, R.; Alemany, R.; Loskog, A. Shaping the Tumor Stroma and Sparking Immune Activation by CD40 and 4-1BB Signaling Induced by an Armed Oncolytic Virus. Clin. Cancer Res. 2017, 23, 5846–5857. [Google Scholar] [CrossRef] [Green Version]
- Koski, A.; Kangasniemi, L.; Escutenaire, S.; Pesonen, S.; Cerullo, V.; Diaconu, I.; Nokisalmi, P.; Raki, M.; Rajecki, M.; Guse, K.; et al. Treatment of cancer patients with a serotype 5/3 chimeric oncolytic adenovirus expressing GMCSF. Mol. Ther. 2010, 18, 1874–1884. [Google Scholar] [CrossRef] [PubMed]
- Ranki, T.; Pesonen, S.; Hemminki, A.; Partanen, K.; Kairemo, K.; Alanko, T.; Lundin, J.; Linder, N.; Turkki, R.; Ristimaki, A.; et al. Phase I study with ONCOS-102 for the treatment of solid tumors—An evaluation of clinical response and exploratory analyses of immune markers. J. Immunother. Cancer 2016, 4, 17. [Google Scholar] [CrossRef] [Green Version]
- Maroun, J.; Munoz-Alia, M.; Ammayappan, A.; Schulze, A.; Peng, K.W.; Russell, S. Designing and building oncolytic viruses. Future Virol. 2017, 12, 193–213. [Google Scholar] [CrossRef] [Green Version]
- Russell, S.J. RNA viruses as virotherapy agents. Cancer Gene Ther. 2002, 9, 961–966. [Google Scholar] [CrossRef]
- Millward, S.; Graham, A.F. Structural studies on reovirus: Discontinuities in the genome. Proc. Natl. Acad. Sci. USA 1970, 65, 422–429. [Google Scholar] [CrossRef] [Green Version]
- Phillips, M.B.; Stuart, J.D.; Rodriguez Stewart, R.M.; Berry, J.T.; Mainou, B.A.; Boehme, K.W. Current understanding of reovirus oncolysis mechanisms. Oncolytic Virother. 2018, 7, 53–63. [Google Scholar] [CrossRef] [Green Version]
- Norman, K.L.; Lee, P.W. Reovirus as a novel oncolytic agent. J. Clin. Investig. 2000, 105, 1035–1038. [Google Scholar] [CrossRef] [Green Version]
- Gong, J.; Mita, M.M. Activated ras signaling pathways and reovirus oncolysis: An update on the mechanism of preferential reovirus replication in cancer cells. Front. Oncol. 2014, 4, 167. [Google Scholar] [CrossRef]
- Clements, D.; Helson, E.; Gujar, S.A.; Lee, P.W. Reovirus in cancer therapy: An evidence-based review. Oncolytic Virother. 2014, 3, 69–82. [Google Scholar] [CrossRef] [Green Version]
- Morris, D.G.; Feng, X.; DiFrancesco, L.M.; Fonseca, K.; Forsyth, P.A.; Paterson, A.H.; Coffey, M.C.; Thompson, B. REO-001: A phase I trial of percutaneous intralesional administration of reovirus type 3 dearing (Reolysin(R)) in patients with advanced solid tumors. Investig. New Drugs 2013, 31, 696–706. [Google Scholar] [CrossRef] [PubMed]
- Vidal, L.; Pandha, H.S.; Yap, T.A.; White, C.L.; Twigger, K.; Vile, R.G.; Melcher, A.; Coffey, M.; Harrington, K.J.; DeBono, J.S. A phase I study of intravenous oncolytic reovirus type 3 Dearing in patients with advanced cancer. Clin. Cancer Res. 2008, 14, 7127–7137. [Google Scholar] [CrossRef] [Green Version]
- Gollamudi, R.; Ghalib, M.H.; Desai, K.K.; Chaudhary, I.; Wong, B.; Einstein, M.; Coffey, M.; Gill, G.M.; Mettinger, K.; Mariadason, J.M.; et al. Intravenous administration of Reolysin, a live replication competent RNA virus is safe in patients with advanced solid tumors. Investig. New Drugs 2010, 28, 641–649. [Google Scholar] [CrossRef] [Green Version]
- 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. 2012, 20, 1998–2003. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Harrington, K.J.; Karapanagiotou, E.M.; Roulstone, V.; Twigger, K.R.; White, C.L.; Vidal, L.; Beirne, D.; Prestwich, R.; Newbold, K.; Ahmed, M.; et al. Two-stage phase I dose-escalation study of intratumoral reovirus type 3 dearing and palliative radiotherapy in patients with advanced cancers. Clin. Cancer Res. 2010, 16, 3067–3077. [Google Scholar] [CrossRef] [Green Version]
- Lolkema, M.P.; Arkenau, H.T.; Harrington, K.; Roxburgh, P.; Morrison, R.; Roulstone, V.; Twigger, K.; Coffey, M.; Mettinger, K.; Gill, G.; 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, 581–588. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- O’Leary, M.P.; Choi, A.H.; Kim, S.I.; Chaurasiya, S.; Lu, J.; Park, A.K.; Woo, Y.; Warner, S.G.; Fong, Y.; Chen, N.G. Novel oncolytic chimeric orthopoxvirus causes regression of pancreatic cancer xenografts and exhibits abscopal effect at a single low dose. J. Transl. Med. 2018, 16, 110. [Google Scholar] [CrossRef]
- Chaurasiya, S.; Chen, N.G.; Lu, J.; Martin, N.; Shen, Y.; Kim, S.I.; Warner, S.G.; Woo, Y.; Fong, Y. A chimeric poxvirus with J2R (thymidine kinase) deletion shows safety and anti-tumor activity in lung cancer models. Cancer Gene Ther. 2020, 27, 125–135. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Choi, A.H.; O’Leary, M.P.; Lu, J.; Kim, S.I.; Fong, Y.; Chen, N.G. Endogenous Akt Activity Promotes Virus Entry and Predicts Efficacy of Novel Chimeric Orthopoxvirus in Triple-Negative Breast Cancer. Mol. Ther. Oncolytics 2018, 9, 22–29. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Chaurasiya, S.; Chen, N.G.; Fong, Y. Oncolytic viruses and immunity. Curr. Opin. Immunol. 2018, 51, 83–90. [Google Scholar] [CrossRef] [PubMed]
Virus | Transgene | Combination | Tumor Type | Phase | Reference |
---|---|---|---|---|---|
G207 | None | Radiation | Brain tumor | II | NCT04482933 |
ONCR-177 | IL-12, CCL4, FLT3LG, αCTLA4 and αPD-1 | pembrolizumab | Melanoma and other solid tumors | I | NCT04348916 |
OH2 (HSV-2) | GM-CSF | Irinotecan or HX008 | Gastrointestinal tumors and other solid tumors | I & II | NCT03866525 |
RP1 | GALV-GP and GM-CSF | None | Cutaneous squamous cell carcinoma | IB | NCT04349436 |
RP1 | GALV-GP and GM-CSF | Cemiplimab | Cutaneous squamous cell carcinoma | I | NCT04050436 |
RP2 | GALV-GP and GM-CSF | Nivolumab | Advanced solid tumors | i | NCT03767348 |
T-VEC | GM-CSF | Ipilimumab and Nivolumab | Breast Cancer | I | NCT04185311 |
T-VEC | GM-CSF | None | Angiosarcoma of skin | II | NCT03921073 |
T-VEC | GM-CSF | Pembrolizumab | Sarcoma | II | NCT03069378 |
T-VEC | GM-CSF | Pembrolizumab | Cutaneous melanoma | II | NCT03842943 |
Virus | Transgene | Combination | Tumor Type | Phase | Status | Reference |
---|---|---|---|---|---|---|
Pexa-Vec | GM-CSF | REGN2810 (anti-PD-1) | Renal cell carcinoma | I | Recruiting | NCT03294083 |
Pexa-Vec | GM-CSF | Ipilimumab | Any except liver cancer | I | Recruiting | NCT02977156 |
Pexa-Vec | GM-CSF | Cyclophosphamide and Avelumab | Solid tumors and soft tissue sarcoma | I & II | Recruiting | NCT02630368 |
Pexa-Vec | GM-CSF | Sorafenib | Hepatocellular carcinoma | II | Completed | NCT01171651 |
Pexa-Vec | GM-CSF | None | Hepatocellular carcinoma | II | Completed | NCT01636284 |
Pexa-Vec | GM-CSF | BSC | Hepatocellular carcinoma | II | Completed | NCT01387555 |
T601 | FCU1 | 5-Fluorocytosine | Solid tumors | I & II | Recruiting | NCT04226066 |
TBio-6517 | FLT3L, IL-12, αCTLA-4 | Pembrolizumab | Solid Tumors | I & II | Recruiting | NCT04301011 |
GL-ONC1 | Luc-GFP, β-Galactosidase β-glucuronidase | Bevacizumab | Ovarian cancer, peritoneal carcinomatosis and cancer of fallopian tube | I & II | Recruiting | NCT02759588 |
GL-ONC1 | Luc-GFP, β-Galactosidase β-glucuronidase | None | Head and neck cancer | I | Completed | NCT01584284 |
GL-ONC1 | Luc-GFP, β-Galactosidase β-glucuronidase | None | Solid tumors | I | Completed | NCT00794131 |
vvDD | Cytosine deaminase and somatostatin receptor | None | Solid tumors | I | Completed | NCT00574977 |
Virus | Transgene | Combination | Tumor Type | Phase | Status | Reference |
---|---|---|---|---|---|---|
LOAd703 | CD40L, 4-1BBL | None | Pancreatic cancer, ovarian cancer, biliary carcinoma, colorectal cancer | 1 & 2 | Recruiting | NCT03225989 |
LOAd703 | CD40L, 4-1BBL | atezolizumab | Malignant Melanoma | 1 & 2 | Recruiting | NCT04123470 |
LOAd703 | CD40L, 4-1BBL | Gemcitabine, nab-paclitaxel and atezolizumab | Pancreatic cancer | 1 & 2 | Recruiting | NCT02705196 |
TILT-123 | hIL-2, TNFa | None | Metaststic melanoma | 1 | Recruiting | NCT04217473 |
DNX-2440 | OX40L | None | Glioblastoma | 1 | Recruiting | NCT03714334 |
CG0070 | GM-CSF | None | Bladder cancer | 2 | Completed | NCT02365818 |
Delta-24-RGD | None | None | Brain tumor | 1 & 2 | Completed | NCT01582516 |
MG1-MAGEA3 | MAGEA3 | Pembrolizumab, Ad-MAGEA3 | NSCLC | 1 & 2 | Completed | NCT02879760 |
Combination | Tumor Type | Phase | Status | Reference |
---|---|---|---|---|
Paclitaxel | Ovarian cancer, peritoneal carcinomatosis and cancer of fallopian tube | 2 | Completed | NCT01199263 |
None | Sarcoma | 2 | Completed | NCT00503295 |
Carboplatin Paclitaxel | NSCLC | 2 | Completed | NCT00861627 |
Irinotecan, Leucovorin, 5-FU, Bevacizumab | Colorectal cancer | 1 | Completed | NCT01274624 |
Carboplatin Paclitaxel | Head and Neck cancer | 3 | Completed | NCT01166542 |
None | Malignant glioma | 1 | Completed | NCT00528684 |
Carboplatin Paclitaxel | Lung Cancer | 2 | Completed | NCT00998192 |
Carboplatin Paclitaxel | Head and neck cancer | 2 | Completed | NCT00753038 |
Carboplatin Paclitaxel | Metastatic melanoma | 2 | Completed | NCT00984464 |
Paclitaxel, Avelumab | Metastatic breast cancer | 2 | Recruiting | NCT04215146 |
Carfilzomib, Dexamethasone, Nivolumab | Recurrent Plasma cell myeloma | 1 | Recruiting | NCT03605719 |
Retifanlimab | TNBC | 2 | Recruiting | NCT04445844 |
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Chaurasiya, S.; Fong, Y.; Warner, S.G. Oncolytic Virotherapy for Cancer: Clinical Experience. Biomedicines 2021, 9, 419. https://doi.org/10.3390/biomedicines9040419
Chaurasiya S, Fong Y, Warner SG. Oncolytic Virotherapy for Cancer: Clinical Experience. Biomedicines. 2021; 9(4):419. https://doi.org/10.3390/biomedicines9040419
Chicago/Turabian StyleChaurasiya, Shyambabu, Yuman Fong, and Susanne G. Warner. 2021. "Oncolytic Virotherapy for Cancer: Clinical Experience" Biomedicines 9, no. 4: 419. https://doi.org/10.3390/biomedicines9040419