Abstract
Oncolytic immunotherapy is a new form of cancer treatment that utilizes native or genetically modified viruses to directly infect tumor cells. These viruses selectively replicate in tumor cells and may induce systemic antitumor immune responses. To date, the herpesviruses have been the most widely evaluated for clinical development as a cancer therapeutic. A modified herpesvirus encoding human granulocyte-macrophage colony-stimulating factor (GM-CSF) has been named talimogene laherparepvec (T-VEC) and has shown clinical benefits in a randomized Phase III clinical trial in patients with advanced melanoma. This chapter will review the basic mechanisms of oncolytic viruses, describe the basic biology of herpesviruses, and discuss the clinical results of trials with T-VEC. Future directions and priorities for clinical development of T-VEC and other oncolytic viruses will be discussed.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Similar content being viewed by others
References
Andtbacka RHI, Collichio F, Amatruda T et al (2013) OPTIM: a randomized phase 3 trial of talimogene laherparepvec (T-VEC) vs subcutaneous (SC) granulocyte-macrophage colony-stimulating factor (GM-CSF) for the treatement of unresectable stage IIIB/C and IV melanoma (abstract). Am Soc Clin Oncol Suppl; abstr LBA9008
Carson WE (2005) Getting melanoma cells to stimulate with frequency. J Clin Oncol 23(35):8929–8931
Disis ML, Bernhard H, Shiota FM et al (1996) Granulocyte-macrophage colony-stimulating factor: an effective adjuvant for protein and peptide-based vaccines. Blood 88(1):202–210
Dranoff G, Jaffee E, Lazenby A et al (1993) Vaccination with irradiated tumor cells engineered to secrete murine granulocyte-macrophage colony-stimulating factor stimulates potent, specific, and long-lasting anti-tumor immunity. Proc Natl Acad Sci U S A 90:3539–3543
Filipazzi P, Valenti R, Huber V et al (2007) Identification of a new subset of myeloid suppressor cells in peripheral blood of melanoma patients with modulation by a granulocyte-macrophage colony-stimulation factor-based antitumor vaccine. J Clin Oncol 25(18):2546–2553
Fong Y, Kim T, Bhargava A et al (2009) A herpes oncolytic virus can be delivered via the vasculature to produce biologic changes in human colorectal cancer. Mol Ther 17(2):389–394
Geevarghese SK, Geller DA, de Haan HA et al (2010) Phase I/II study of oncolytic herpes simplex virus NV1020 in patients with extensively pretreated refractory colorectal cancer metastatic to the liver. Hum Gene Ther 21(9):1119–1128
Grotz TE, Kottschade L, Pavey ES, Markovic SN, Jakub JW (2014) Adjuvant GM-CSF improves survival in high-risk stage IIIc melanoma-a single-center study. Am J Clin Oncol 37(5):467–72
Harrington KJ, Hingorani M, Tanay M et al (2010) Phase I/II study of oncolytic HSVGM-CSF in combination with radiotherapy and cisplatin in untreated stage III/IV squamous cell cancer of the head and neck. Clin Cancer Res 16(15):4005–4015
Harrow S, Papanastassiou V, Harland J et al (2004) HSV1716 injection into the brain adjacent to tumour following surgical resection of high-grade glioma: safety data and long-term survival. Gene Ther 11(22):1648–1658
Hu JC, Coffin RS, Davis CJ et al (2006) A phase I study of OncoVexGM-CSF, a second-generation oncolytic herpes simplex virus expressing granulocyte macrophage colony-stimulating factor. Clin Cancer Res 12(22):6737–6747
Jinushi M, Nakazaki Y, Dougan M, Carrasco D, Mihm M, Dranoff G (2007) MFG-E8-mediated uptake of apoptotic cells by APCs links the pro- and anti-inflammatory activities of GM-CSF. J Clin Invest 117:1902–1913
Kaufman HL, Bines SD (2010) The OPTiM trial: a phase III prospective randomized clinical trial of an oncolytic herpesvirus encoding GM-CSF in patients with unresectable stage III or IV melanoma. Future Oncol 6(6):941–949
Kaufman HL, Kim DW, DeRaffele G, Mitcham J, Coffin RS, Kim-Schulze S (2010) Local and distant immunity induced by intralesional vaccination with an oncolytic herpes virus encoding GM-CSF in patients with stage IIIc and IV melanoma. Ann Surg Oncol 17:718–730
Kemeny N, Brown K, Covey A et al (2006) Phase I, open-label, dose-escalating study of a genetically engineered herpes simplex virus, NV1020, in subjects with metastatic colorectal carcinoma to the liver. Hum Gene Ther 17(12):1214–1224
Kimata H, Imai T, Kikumori T et al (2006) Pilot study of oncolytic viral therapy using mutant herpes simplex virus (HF10) against recurrent metastatic breast cancer. Ann Surg Oncol 13(8):1078–1084
Liu BL et al (2003) ICP34.5 deleted herpes simplex virus with enhanced oncolytic, immune stimulating and anti-tumour properties. Gene Ther 10:292–303
Markert JM, Liechty PG, Wang W et al (2009) Phase Ib trial of mutant herpes simplex virus G207 inoculated pre- and post-tumor resection for recurrent GBM. Mol Ther 17(1):199–207
Papanastassiou V, Rampling R, Frasher M et al (2002) The potential for efficacy of the modified (ICP 34.5(−)) herpes simplex virus HSV 1716 following intratumoural injection into human malignant glioma: a proof of principle study. Gene Ther 9(6):398–406
Pawlik TM, Nakamura H, Yoon SS et al (2000) Oncolysis of diffuse hepatocellular carcinoma by intravascular administration of a replication-competent, genetically engineered herpesvirus. Cancer Res 60(11):2790–2795
Rampling R, Cruickshank G, Papanastassio V et al (2007) Toxicity evaluation of replication-competent herpes simplex virus (ICP 34.5 null mutant 1716) in patients with recurrent malignant glioma. Gene Ther 7(10):859–866
Senzer NN, Kaufman HL, Amatruda T et al (2009) 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 27(34):5763–5771
Serafini P, De Santo C, Marigo I et al (2004a) Derangement of immune response by myeloid suppressor cells. Cancer Immunol Immunother 53:64–82
Serafini P, Carbley R, Noonan KA, Tan G, Bronte V, Borrello I (2004b) High-dose granulocyte-macrophage colony-stimulating factor-producing vaccines impair the immune response through the recruitment of myeloid suppressor cells. Cancer Res 64:6337–6343
Slingluff CL, Petroni GR, Yamshchikov GV et al (2003) Clinical and immunologic results of a randomized phase II trial of vaccination using four melanoma peptides either administered in granulocyte-macrophage colony-stimulating factor in adjuvant or pulsed on dendritic cells. J Clin Oncol 21(21):4016–4026
Slingluff CL, Petroni GR, Olson WC et al (2009) Effect of granulocyte/macrophage colony-stimulating factor on circulating CD8+ and CD4+ T-cell responses to a multipeptide melanoma vaccine: outcome of a multicenter randomized trial. Clin Cancer Res 15:7036–7044
Small EJ, Fratesi P, Reese DM et al (2000) Immunotherapy of hormone-refractory prostate cancer with antigen-loaded dendritic cells. J Clin Oncol 18(23):3894–3903
Small EJ, Schellhammer PF, Higano CS et al (2006) Placebo-controlled phase III trial of immunologic therapy with sipuleucel-T (APC8015) in patients with metastatic, asymptomatic hormone refractory prostate cancer. J Clin Oncol 24(19):3089–3094
Spitler LE, Grossbard ML, Ernstoff MS et al (2000) Adjuvant therapy of stage III and IV malignant melanoma using granulocyte-macrophage colony-stimulating factor. J Clin Oncol 18(8):1614–1621
Spitler LE, Weber RW, Allen RE et al (2009) Recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF, sargramostim) administered for 3 years as adjuvant therapy of stages II (T4), III, and IV melanoma. J Immunother 32(6):632–637
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2014 Springer-Verlag Wien
About this chapter
Cite this chapter
Hughes, T., Kaufman, H.L. (2014). The Use of Oncolytic Herpesvirus for the Treatment of Cancer. In: Lukashevich, I., Shirwan, H. (eds) Novel Technologies for Vaccine Development. Springer, Vienna. https://doi.org/10.1007/978-3-7091-1818-4_11
Download citation
DOI: https://doi.org/10.1007/978-3-7091-1818-4_11
Published:
Publisher Name: Springer, Vienna
Print ISBN: 978-3-7091-1817-7
Online ISBN: 978-3-7091-1818-4
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)