Skip to main content
SpringerLink
Log in
SpringerLink
Log in

Oncolytic Virotherapy by HSV

  • Chapter
  • First Online:
Human Herpesviruses

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1045))

Abstract

Oncolytic virotherapy is a kind of antitumor therapy using viruses with natural or engineered tumor-selective replication to intentionally infect and kill tumor cells. An early clinical trial has been performed in the 1950s using wild-type and non-engineered in vitro-passaged virus strains and vaccine strains (first generation oncolytic viruses). Because of the advances in biotechnology and virology, the field of virotherapy has rapidly evolved over the past two decades and innovative recombinant selectivity-enhanced viruses (second generation oncolytic viruses). Nowadays, therapeutic transgene-delivering “armed” oncolytic viruses (third generation oncolytic viruses) have been engineered using many kinds of viruses. In this chapter, the history, mechanisms, rationality, and advantages of oncolytic virotherapy by herpes simplex virus (HSV) are mentioned. Past and ongoing clinical trials by oncolytic HSVs (G207, HSV1716, NV1020, HF10, Talimogene laherparepvec (T-VEC, OncoVEXGM-CSF)) are also summarized. Finally, the way of enhancement of oncolytic virotherapy by gene modification or combination therapy with radiation, chemotherapy, or immune checkpoint inhibitors are discussed.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 189.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 249.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 249.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Advani SJ, Chung SM, Yan SY et al (1999) Replication-competent, nonneuroinvasive genetically engineered herpes virus is highly effective in the treatment of therapy-resistant experimental human tumors. Cancer Res 59:2055–2058

    PubMed  CAS  Google Scholar 

  • Andtbacka RH, Kaufman HL, Collichio F et al (2015) Talimogene laherparepvec improves durable response rate in patients with advanced melanoma. J Clin Oncol 33:2780–2788

    Article  CAS  Google Scholar 

  • Bataille D, Epstein AL (1995) Herpes simplex virus type 1 replication and recombination. Biochimie 77:787–795

    Article  PubMed  CAS  Google Scholar 

  • Boehmer PE, Nimonkar AV (2003) Herpes virus replication. IUBMB Life 55:3–22

    Article  Google Scholar 

  • Braidwood L, Graham SV, Graham A et al (2013) Oncolytic herpes viruses, chemotherapeutics, and other cancer drugs. Oncolytic Virother 2:57–74

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Bringhurst RM, Schaffer PA (2006) Cellular stress rather than stage of the cell cycle enhances the replication and plating efficiencies of herpes simplex virus type 1 ICP0- viruses. J Virol 80:4528–4537

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Cozzi PJ, Malhotra S, Mcauliffe P et al (2001) Intravesical oncolytic viral therapy using attenuated, replication-competent herpes simplex viruses G207 and Nv1020 is effective in the treatment of bladder cancer in an orthotopic syngeneic model. FASEB J 15:1306–1308

    Article  PubMed  CAS  Google Scholar 

  • DePace NG (1912) Sulla Scomparsa di un enorme cancro begetante del callo dell’utero senza cura chirurgica [Italian]. Ginecol 9:82

    Google Scholar 

  • Dock G (1904) Influence of complicating diseases upon leukemia. Am J Med Sci 127:563–592

    Article  Google Scholar 

  • Dossett LA, Kudchadkar RR, Zager JS (2015) BRAF and MEK inhibition in melanoma. Expert Opin Drug Saf 14:559–570

    Article  PubMed  CAS  Google Scholar 

  • Ebright MI, Zager JS, Malhotra S et al (2002) Replication-competent herpes virus NV1020 as direct treatment of pleural cancer in a rat model. J Thorac Cardiovasc Surg 124:123–129

    Article  PubMed  Google Scholar 

  • Esaki S, Goshima F, Kimura H et al (2013) Enhanced antitumoral activity of oncolytic herpes simplex virus with gemcitabine using colorectal tumor models. Int J Cancer 132:1592–1601

    Article  PubMed  CAS  Google Scholar 

  • Fu X, Zhang X (2002) Potent systemic antitumor activity from an oncolytic herpes simplex virus of syncytial phenotype. Cancer Res 62:2306–2312

    PubMed  CAS  Google Scholar 

  • Fujimoto Y, Mizuno T, al SS (2006) Intratumoral injection of herpes simplex virus HF10 in recurrent head and neck squamous cell carcinoma. Acta Otolaryngol 126:1115–1117

    Article  PubMed  Google Scholar 

  • Gambini E, Reisoli E, Appolloni I et al (2012) Replication-competent herpes simplex virus retargeted to HER2 as therapy for high-grade glioma. Mol Ther 20:994–1001

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • 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 21:1119–1128

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Harrington KJ, Hingorani M, Tanay MA et al (2010) Phase I/II study of oncolytic HSV GM-CSF in combination with radiotherapy and cisplatin in untreated stage III/IV squamous cell cancer of the head and neck. Clin Cancer Res 16:4005–4015

    Article  PubMed  CAS  Google Scholar 

  • 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 11:1648–1658

    Article  PubMed  CAS  Google Scholar 

  • Hill A, Jugovic P, York I et al (1995) Herpes simplex virus turns off the TAP to evade host immunity. Nature 375:411–415

    Article  PubMed  CAS  Google Scholar 

  • Hu JCC, Coffin RS, Davis CJ (2006) A phase I study of OncoVEXGM-CSF, a second-generation oncolytic herpes simplex virus expressing granulocyte macrophage colony-stimulating factor. Clin Cancer Res 12:6737–6747

    Article  PubMed  CAS  Google Scholar 

  • Huebner RJ, Rowe WP, Schatten WE et al (1956) Studies on the use of viruses in the treatment of carcinoma of the cervix. Cancer 9:1211–1218

    Article  PubMed  CAS  Google Scholar 

  • Hummel JL, Safroneeva E, Mossman KL (2005) The role of ICP0-Null HSV-1 and interferon signaling defects in the effective treatment of breast adenocarcinoma. Mol Ther 12:1101–1110

    Article  PubMed  CAS  Google Scholar 

  • Jackson C, Browell D, Gautrey H et al (2013) Clinical significance of HER-2 splice variants in breast cancer progression and drug resistance. Int J Cell Biol 2013:973584

    Article  PubMed  PubMed Central  Google Scholar 

  • Jones C, Inman M, Peng W et al (2005) The herpes simplex virus type 1 locus that encodes the latency-associated transcript enhances the frequency of encephalitis in male BALB/c mice. J Virol 79:14465–14469

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Kanai R, Zaupa C, Sgubin D et al (2012) Effect of γ34.5 deletions on oncolytic herpes simplex virus activity in brain tumors. J Virol 86:4420–4431

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Kaufman HL, Kim DW, DeRaffele G et al (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

    Article  PubMed  Google Scholar 

  • 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 17:1214–1224

    Article  PubMed  CAS  Google Scholar 

  • Kimata H, Takakuwa H, Goshima F et al (2003) Effective treatment of disseminated peritoneal colon cancer with new replication-competent herpes simplex viruses. Hepato-Gastroenterology 50:961–966

    PubMed  Google Scholar 

  • 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 13:1078–1084

    Article  PubMed  Google Scholar 

  • Kohno S, Luo C, Goshima F et al (2005) Herpes simplex virus type 1 mutant HF10 oncolytic viral therapy for bladder cancer. Urology 66:1116–1121

    Article  PubMed  Google Scholar 

  • Kohno SI, Luo C, Nawa A et al (2007) Oncolytic virotherapy with an HSV amplicon vector expressing granulocyte-macrophage colony-stimulating factor using the replication-competent HSV type 1 mutant HF10 as a helper virus. Cancer Gene Ther 14:918–926

    Article  PubMed  CAS  Google Scholar 

  • Kong Y, Yang T, Geller AI (1999) An efficient in vivo recombination cloning procedure for modifying and combining HSV-1 cosmids. J Virol Methods 80:129–136

    Article  PubMed  CAS  Google Scholar 

  • Koshizuka T, Kawaguchi Y, Nishiyama Y (2005) Herpes simplex virus type 2 mem- brane protein UL56 associates with the kinesin motor protein KIF1A. J Gen Virol 86:527–533

    Article  PubMed  CAS  Google Scholar 

  • Lilley CE, Carson CT, Muotri AR et al (2005) DNA repair proteins affect the lifecycle of herpes simplex virus 1. Proc Natl Acad Sci U S A 102:5844–5849

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Liu BL, Robinson M, Han ZQ et al (2003) ICP34.5 deleted herpes simplex virus with enhanced oncolytic, immune stimulating, and anti-tumour properties. Gene Ther 10:292–303

    Article  PubMed  CAS  Google Scholar 

  • MacKie RM, Stewart B, Brown SM (2001) Intralesional injection of herpes simplex virus 1716 in metastatic melanoma. Lancet 357:525–526

    Article  PubMed  CAS  Google Scholar 

  • 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 17:199–207

    Article  PubMed  CAS  Google Scholar 

  • Markert JM, Razdan SN, Kuo HC et al (2014) A phase 1 trial of oncolytic HSV-1, G207, given in combination with radiation for recurrent GBM demonstrates safety and radiographic responses. Mol Ther 22:1048–1055

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Martuza RL, Malick A, Markert JM et al (1991) Experimental therapy of human glioma by means of a genetically engineered virus mutant. Science 252:854–885

    Article  PubMed  CAS  Google Scholar 

  • Marconi P, Argnani R, Berto E et al (2008) HSV as a vector in vaccine development and gene therapy. Hum Vaccin 4:91–105

    Article  PubMed  CAS  Google Scholar 

  • McGeoch DJ, Dalrymple MA, Davison AJ et al (1988) The complete DNA sequence of the long unique region in the genome of herpes simplex virus type 1. J Gen Virol 69:1531–1574

    Article  PubMed  CAS  Google Scholar 

  • Menotti L, Cerretani A, Hengel H et al (2008) Construction of a fully retargeted herpes simplex virus 1 recombinant capable of entering cells solely via human epidermal growth factor receptor 2. J Virol 82(20):10153–10161

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Mineta T, Rabkin SD, Yazaki T et al (1995) Attenuated multi-mutated herpes simplex virus-1 for the treatment of malignant gliomas. Nat Med 1:938–943

    Article  PubMed  CAS  Google Scholar 

  • Mori I, Nishiyama Y (2005) Herpes simplex virus and varicella-zoster virus: why do these human alphaherpesviruses behave so differently from one another? Rev Med Virol 15:393–406

    Article  PubMed  CAS  Google Scholar 

  • Mori I, Nishiyama Y (2006) Accessory genes define the relationship between the herpes simplex virus and its host. Microbes Infect 8:2556–2562

    Article  PubMed  CAS  Google Scholar 

  • Mullerad M, Bochner BH, Adusumilli PS et al (2005) Herpes simplex virus based gene therapy enhances the efficacy of mitomycin C for the treatment of human bladder transitional cell carcinoma. J Urol 174:741–746

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Nakamura H, Mullen JT, Chandrasekhar S et al (2001) Multimodality therapy with a replication-conditional herpes simplex virus 1 mutant that expresses yeast cytosine deaminase for intratumoral conversion of 5-fluorocytosine to 5-fluorouracil. Cancer Res 61:5447–5452

    PubMed  CAS  Google Scholar 

  • Nakao A, Kimata H, al IT (2004) Intratumoral injection of herpes simplex virus HF10 in recurrent breast cancer. Ann Oncol 15:988–989

    Article  PubMed  CAS  Google Scholar 

  • Nakashima H, Chiocca EA (2014) Modification of HSV-1 to an oncolytic virus. Methods Mol Biol 1144:117–127

    Article  PubMed  Google Scholar 

  • Nanni P, Gatta V, Menotti L et al (2013) Preclinical therapy of disseminated HER-2+ ovarian and breast carcinomas with a HER-2-retargeted oncolytic herpesvirus. PLoS Pathog 9:e1003155

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Nawa A, Luo C, Zhang L et al (2008) Non- engineered, naturally oncolytic herpes simplex virus HSV1 HF-10: applications for cancer gene therapy. Curr Gene Ther 8:208–221

    Article  PubMed  CAS  Google Scholar 

  • Nishiyama Y (1996) Herpesvirus genes: molecular basis of viral replication and pathogenicity. Nagoya J Med Sci 59:107–119

    PubMed  CAS  Google Scholar 

  • Nishiyama Y (2004) Herpes simplex virus gene products: the accessories reflect her lifestyle well. Rev Med Virol 14:33–46

    Article  PubMed  CAS  Google Scholar 

  • Nishiyama Y, Kimura H, Daikoku T (1991) Complementary lethal invasion of the central nervous system by nonneuroinvasive herpes simplex virus types 1 and 2. J Virol 65:4520–4524

    PubMed Central  PubMed  CAS  Google Scholar 

  • Pérez-Herrero E, Fernández-Medarde A (2015) Advanced targeted therapies in cancer: drug nanocarriers, the future of chemotherapy. Eur J Pharm Biopharm 93:52–79

    Article  PubMed  CAS  Google Scholar 

  • Pourchet A, Fuhrmann SR, Pilones KA et al (2016) CD8(+) T-cell immune evasion enables oncolytic virus immunotherapy. EBioMedicine 5:59–67

    Article  PubMed  PubMed Central  Google Scholar 

  • Puzanov I, Milhem MM, Minor D et al (2016) Talimogene laherparepvec in combination with ipilimumab in previously untreated, unresectable stage IIIB-IV melanoma. J Clin Oncol 34:2619–2626

    Article  PubMed  CAS  Google Scholar 

  • Salameh S, Sheth U, Shukla D (2012) Early events in herpes simplex virus lifecycle with implications for an infection of lifetime. Open Virol J 6:1–6

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Sengupta S, Thaci B, Crawford AC et al (2014) Interleukin-13 receptor alpha 2-targeted glioblastoma immunotherapy. Biomed Res Int 2014:952128

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • 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 27:5763–5771

    Article  PubMed  CAS  Google Scholar 

  • Sobol PT, Mossman KL (2006) ICP0 prevents RNase L-independent rRNA cleavage in herpes simplex virus type 1-infected cells. J Virol 80:218–225

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Spain L, Diem S, Larkin J (2016) Management of toxicities of immune checkpoint inhibitors. Cancer Treat Rev 44:51–60

    Article  PubMed  CAS  Google Scholar 

  • Spear MA, Sun F, Eling DJ et al (2000) Cytotoxicity, apoptosis, and viral replication in tumor cells treated with oncolytic ribonucleotide reductase-defective herpes simplex type 1 virus (hrR3) combined with ionizing radiation. Cancer Gene Ther 7:1051–1059

    Article  PubMed  CAS  Google Scholar 

  • Stanziale SF, Petrowsky H, Adusumilli PS et al (2004) Infection with oncolytic herpes simplex virus-1 induces apoptosis in neighboring human cancer cells: a potential target to increase anticancer activity. Clin Cancer Res 10:3225–3232

    Article  PubMed  CAS  Google Scholar 

  • Stavropoulos TA, Strathdee CA (1998) An enhanced packaging system for helper- dependent herpes simplex virus vectors. J Virol 72:7137–7143

    PubMed Central  PubMed  CAS  Google Scholar 

  • Stiles BM, Adusumilli PS, Bhargava A et al (2006a) Minimally invasive localization of oncolytic herpes simplex viral therapy of metastatic pleural cancer. Cancer Gene Ther 13:53–64

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Stiles BM, Adusumilli PS, Stanziale SF et al (2006b) Estrogen enhances the efficacy of an oncolytic HSV-1 mutant in the treatment of estrogen receptor-positive breast cancer. Int J Oncol 28:1429–1439

    PubMed Central  PubMed  CAS  Google Scholar 

  • Sundaresan P, Hunter WD, Martuza RL et al (2000) Attenuated, replication-competent herpes simplex virus type 1 mutant G207: safety evaluation in mice. J Virol 74:3832–3841

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Sze DY, Iagaru AH, Gambhir SS et al (2012) Response to intra-arterial oncolytic virotherapy with the herpes virus NV1020 evaluated by [18F]fluorodeoxyglucose positron emission tomography and computed tomography. Hum Gene Ther 23:91–97

    Article  PubMed  CAS  Google Scholar 

  • Sze DY, Reid TR, Rose SC (2013) Oncolytic virotherapy. J Vasc Interv Radiol 24:1115–1122

    Article  PubMed  Google Scholar 

  • Takakuwa H, Goshima F, Nozawa N et al (2003) Oncolytic viral therapy using a spontaneously generated herpes simplex virus type 1 variant for disseminated peritoneal tumor in immunocompetent mice. Arch Virol 148:813–825

    Article  PubMed  CAS  Google Scholar 

  • Tanaka M, Kagawa H, Yamanashi Y et al (2003) Construction of an excisable bacterial artificial chromosome containing a full-length infectious clone of herpes simplex virus type 1: viruses reconstituted from the clone exhibit wild-type properties in vitro and in vivo. J Virol 77:1382–1391

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Tang T, Eldabaje R, Yang L (2016) Current status of biological therapies for the treatment of metastatic melanoma. Anticancer Res 36:3229–3241

    Article  PubMed  CAS  Google Scholar 

  • Taylor TJ, Brockman MA, McNamee EE et al (2002) Herpes simplex virus. Front Biosci 7:d752–d764

    Article  PubMed  CAS  Google Scholar 

  • Teshigahara O, Goshima F, Takao K et al (2004) Oncolytic viral therapy for breast cancer with herpes simplex virus type 1 mutant HF 10. J Surg Oncol 85:42–47

    Article  PubMed  CAS  Google Scholar 

  • Todo T (2008) Oncolytic virus therapy using genetically engineered herpes simplex viruses. Front Biosci 200813:2060–2064

    Article  Google Scholar 

  • Todo T, Feigenbaum F, Rabkin SD et al (2000) Viral shedding and biodistribution of G207, a multimutated, conditionally replicating herpes simplex virus type 1, after intracerebral inoculation in aotus. Mol Ther 2:588–595

    Article  PubMed  CAS  Google Scholar 

  • Toyoizumi T, Mick R, Abbas AE et al (1999) Combined therapy with chemotherapeutic agents and herpes simplex virus type 1 ICP34.5 mutant (HSV-1716) in human non- small cell lung cancer. Hum Gene Ther 10:3013–3029

    Article  PubMed  CAS  Google Scholar 

  • Ushijima Y, Luo C, Goshima F et al (2007) Determination and analysis of the DNA sequence of highly attenuated herpes simplex virus type 1 mutant HF10, a potential oncolytic virus. Microbes Infect 9:142–149

    Article  PubMed  CAS  Google Scholar 

  • Watanabe D, Goshima F, Mori I et al (2008) Oncolytic virotherapy for malignant melanoma with herpes simplex virus type 1 mutant HF10. J Dermatol Sci 50:185–196

    Article  PubMed  CAS  Google Scholar 

  • Witt MN, Braun GS, Ihrler S et al (2009) Occurrence of HSV-1-induced pneumonitis in patients under standard immunosuppressive therapy for rheumatic, vasculitic, and connective tissue disease. BMC Pulm Med 18:22

    Article  CAS  Google Scholar 

  • Zabierowski SE, Deluca NA (2008) Stabilized binding of TBP to the TATA box of herpes simplex virus type 1 early (tk) and late (gC) promoters by TFIIA and ICP4. J Virol 82:3546–3554

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Zhou G, Roizman B (2006) Construction and properties of a herpes simplex virus 1 designed to enter cells solely via the IL-13alpha2 receptor. Proc Natl Acad Sci U S A 103:5508–5513

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Zhou G, Ye GJ, al DW (2002) Engineered herpes simplex virus 1 is dependent on IL13Ralpha 2 receptor for cell entry and independent of glycoprotein D receptor interaction. Proc Natl Acad Sci U S A 99:15124–15129

    Article  PubMed  CAS  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Dermatology, Aichi Medical University School of Medicine, Nagakute, Japan

    Daisuke Watanabe

  2. Department of Virology, Graduate School of Medicine, Nagoya University, Nagoya, Japan

    Fumi Goshima

Authors
  1. Daisuke Watanabe
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Fumi Goshima
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Daisuke Watanabe .

Editor information

Editors and Affiliations

  1. Division of Molecular Virology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo, Japan

    Yasushi Kawaguchi

  2. Division of Clinical Virology, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan

    Yasuko Mori

  3. Department of Virology, Nagoya University Graduation School of Medicine, Nagoya, Aichi, Japan

    Hiroshi Kimura

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer Nature Singapore Pte Ltd.

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Watanabe, D., Goshima, F. (2018). Oncolytic Virotherapy by HSV. In: Kawaguchi, Y., Mori, Y., Kimura, H. (eds) Human Herpesviruses. Advances in Experimental Medicine and Biology, vol 1045. Springer, Singapore. https://doi.org/10.1007/978-981-10-7230-7_4

Download citation

Publish with us

Policies and ethics

Search

Navigation