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  • Review Article
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Viroimmunotherapy for breast cancer: promises, problems and future directions

Abstract

Virotherapy, a strategy to use live viruses as therapeutics, is a relatively novel field in the treatment of cancer. With the advancements in molecular biology and virology, there has been a huge increase in research on cancer virotherapy. For the treatment of cancer, viruses could be used either as vectors in gene therapy or as oncolytic agents. A variety of viruses have been studied for their potential usage in gene therapy or oncolytic therapy. In this review, we discuss virotherapy with a special focus on breast cancer. Breast cancer is the most common cancer and the leading cause of cancer-related deaths in women worldwide. Current treatments are insufficient to cure metastatic breast cancer and are often associated with severe side effects that further deteriorates patients’ quality of life. Therefore, novel therapeutic approaches such as virotherapy need to be developed for the treatment of breast cancer. Here we summarize the current treatments for breast cancer and the potential use of virotherapy in the treatment of the disease. Furthermore, we discuss the use of oncolytic viruses as immunotherapeutics and the rational combination of oncolytic viruses with other therapeutics for optimal treatment of breast cancer. Finally, we outline the progress made in virotherapy for breast cancer and the shortcomings that need to be addressed for this novel therapy to move to the clinic for better treatment of breast cancer.

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Fig. 1: Mechanism of action of oncolytic viruses.

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References

  1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68:394–424.

    Article  PubMed  Google Scholar 

  2. Higgins MJ, Wolff AC. Therapeutic options in the management of metastatic breast cancer. Oncology. 2008;22:614–23.

    PubMed  Google Scholar 

  3. Lu J, Steeg PS, Price JE, Krishnamurthy S, Mani SA, Reuben J, et al. Breast cancer metastasis: challenges and opportunities. Cancer Res. 2009;69:4951–3.

    Article  CAS  PubMed  Google Scholar 

  4. Polyak K. Breast cancer: origins and evolution. J Clin Invest. 2007;117:3155–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Malhotra GK, Zhao X, Band H, Band V. Histological, molecular and functional subtypes of breast cancers. Cancer Biol Ther. 2010;10:955–60.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Cancer Genome Atlas Network. Comprehensive molecular portraits of human breast tumours. Nature. 2012;490:61–70.

    Article  CAS  Google Scholar 

  7. Perou CM, Sorlie T, Eisen MB, van de Rijn M, Jeffrey SS, Rees CA, et al. Molecular portraits of human breast tumours. Nature. 2000;406:747–52.

    Article  CAS  PubMed  Google Scholar 

  8. Sorlie T, Wang Y, Xiao C, Johnsen H, Naume B, Samaha RR, et al. Distinct molecular mechanisms underlying clinically relevant subtypes of breast cancer: gene expression analyses across three different platforms. BMC Genomics. 2006;7:127.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  9. Sorlie T, Perou CM, Tibshirani R, Aas T, Geisler S, Johnsen H, et al. Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci USA. 2001;98:10869–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Burstein HJ, Morrow M. Nodal irradiation after breast-cancer surgery in the era of effective adjuvant therapy. N. Engl J Med. 2015;373:379–81.

    Article  CAS  PubMed  Google Scholar 

  11. Fisher B, Jeong JH, Anderson S, Bryant J, Fisher ER, Wolmark N. Twenty-five-year follow-up of a randomized trial comparing radical mastectomy, total mastectomy, and total mastectomy followed by irradiation. N Engl J Med. 2002;347:567–75.

    Article  PubMed  Google Scholar 

  12. Cotlar AM, Dubose JJ, Rose DM. History of surgery for breast cancer: radical to the sublime. Curr Surg. 2003;60:329–37.

    Article  PubMed  Google Scholar 

  13. Anampa J, Makower D, Sparano JA. Progress in adjuvant chemotherapy for breast cancer: an overview. BMC Med. 2015;13:195.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  14. White J, Achuthan R, Turton P, Lansdown M. Breast conservation surgery: state of the art. Int J Breast Cancer. 2011;2011:107981.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Jin X, Mu P. Targeting breast cancer metastasis. Breast Cancer (Auckl). 2015;9:23–34.

    Google Scholar 

  16. Gupta GP, Massague J. Cancer metastasis: building a framework. Cell 2006;127:679–95.

    Article  CAS  PubMed  Google Scholar 

  17. Ciccone E, Viale O, Bottino C, Pende D, Migone N, Casorati G, et al. Antigen recognition by human T-cell receptor positive-gamma lymphocytes - specific lysis of allogeneic cells after activation in mixed lymphocyte culture. J Exp Med. 1988;167:1517–22.

    Article  CAS  PubMed  Google Scholar 

  18. Hudis CA, Dang CT. Adjuvant therapy for breast cancer: practical lessons from the early breast cancer trialists’ collaborative group. Breast Dis. 2004;21:3–13.

    Article  PubMed  Google Scholar 

  19. Clarke M. Meta-analyses of adjuvant therapies for women with early breast cancer: the Early Breast Cancer Trialists’ Collaborative Group overview. Ann Oncol. 2006;17:x59–62.

    Article  PubMed  Google Scholar 

  20. Vallis KA, Tannock IF. Postoperative radiotherapy for breast cancer: growing evidence for an impact on survival. J Natl Cancer Inst. 2004;96:88–9.

    Article  PubMed  Google Scholar 

  21. Nabholtz JM, Gligorov J. The role of taxanes in the treatment of breast cancer. Expert Opin Pharmacother. 2005;6:1073–94.

    Article  CAS  PubMed  Google Scholar 

  22. Jones SE. Metastatic breast cancer: the treatment challenge. Clin Breast Cancer. 2008;8:224–33.

    Article  CAS  PubMed  Google Scholar 

  23. Early Breast Cancer Trialists’ Collaborative Group. Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet. 2005;365:1687–717.

    Article  CAS  Google Scholar 

  24. Zhao M, Ramaswamy B. Mechanisms and therapeutic advances in the management of endocrine-resistant breast cancer. World J Clin Oncol. 2014;5:248–62.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Slamon D, Eiermann W, Robert N, Pienkowski T, Martin M, Press M, et al. Adjuvant trastuzumab in HER2-positive breast cancer. N. Engl J Med. 2011;365:1273–83.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Baselga J, Perez EA, Pienkowski T, Bell R. Adjuvant trastuzumab: a milestone in the treatment of HER-2-positive early breast cancer. Oncologist 2006;11:4–12.

    Article  CAS  PubMed  Google Scholar 

  27. Jelovac D, Wolff AC. The adjuvant treatment of HER2-positive breast cancer. Curr Treat Options Oncol. 2012;13:230–9.

    Article  PubMed  Google Scholar 

  28. Anders C, Carey LA. Understanding and treating triple-negative breast cancer. Oncology. 2008;22:1233–9.

    PubMed  Google Scholar 

  29. Carey LA, Dees EC, Sawyer L, Gatti L, Moore DT, Collichio F, et al. The triple negative paradox: primary tumor chemosensitivity of breast cancer subtypes. Clin Cancer Res. 2007;13:2329–34.

    Article  CAS  PubMed  Google Scholar 

  30. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell 2011;144:646–74.

    Article  CAS  PubMed  Google Scholar 

  31. Cross D, Burmester JK. Gene therapy for cancer treatment: past, present and future. Clin Med Res. 2006;4:218–27.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Zarogoulidis P, Darwiche K, Sakkas A, Yarmus L, Huang H, Li Q, et al. Suicide Gene Therapy for Cancer - Current Strategies. J Genet Syndr Gene Ther. 2013;4:16849.

  33. Majumdar AS, Zolotorev A, Samuel S, Tran K, Vertin B, Hall-Meier M, et al. Efficacy of herpes simplex virus thymidine kinase in combination with cytokine gene therapy in an experimental metastatic breast cancer model. Cancer Gene Ther. 2000;7:1086–99.

    Article  CAS  PubMed  Google Scholar 

  34. Brockstedt DG, Diagana M, Zhang Y, Tran K, Belmar N, Meier M, et al. Development of anti-tumor immunity against a non-immunogenic mammary carcinoma through in vivo somatic GM-CSF, IL-2, and HSVtk combination gene therapy. Mol Ther. 2002;6:627–36.

    CAS  PubMed  Google Scholar 

  35. Pandha HS, Martin LA, Rigg A, Hurst HC, Stamp GW, Sikora K, et al. Genetic prodrug activation therapy for breast cancer: A phase I clinical trial of erbB-2-directed suicide gene expression. J Clin Oncol. 1999;17:2180–9.

    Article  CAS  PubMed  Google Scholar 

  36. Braybrooke JP, Slade A, Deplanque G, Harrop R, Madhusudan S, Forster MD, et al. Phase I study of MetXia-P450 gene therapy and oral cyclophosphamide for patients with advanced breast cancer or melanoma. Clin Cancer Res. 2005;11:1512–20.

    Article  CAS  PubMed  Google Scholar 

  37. Zheng L, Weilun Z, Minghong J, Yaxi Z, Shilian L, Yanxin L, et al. Adeno-associated virus-mediated doxycycline-regulatable TRAIL expression suppresses growth of human breast carcinoma in nude mice. BMC Cancer. 2012;12:153.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  38. Li YM, Wen Y, Zhou BP, Kuo HP, Ding Q, Hung MC. Enhancement of Bik antitumor effect by Bik mutants. Cancer Res. 2003;63:7630–3.

    CAS  PubMed  Google Scholar 

  39. Bargou RC, Wagener C, Bommert K, Mapara MY, Daniel PT, Arnold W, et al. Overexpression of the death-promoting gene bax-alpha which is downregulated in breast cancer restores sensitivity to different apoptotic stimuli and reduces tumor growth in SCID mice. J Clin Invest. 1996;97:2651–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Rakkar AN, Katayose Y, Kim M, Craig C, Ohri E, Li Z, et al. A novel adenoviral vector expressing human Fas/CD95/APO-1 enhances p53-mediated apoptosis. Cell Death Differ. 1999;6:326–33.

    Article  CAS  PubMed  Google Scholar 

  41. Ogawa T, Kusumoto M, Mizumoto K, Sato N, Tanaka M. Adenoviral GM-CSF gene transduction into breast cancer cells induced long-lasting antitumor immunity in mice. Breast Cancer. 1999;6:301–4.

    Article  CAS  PubMed  Google Scholar 

  42. Chaurasiya S, Hew P, Crosley P, Sharon D, Potts K, Agopsowicz K, et al. Breast cancer gene therapy using an adenovirus encoding human IL-2 under control of mammaglobin promoter/enhancer sequences. Cancer Gene Ther. 2016;23:178–87.

    Article  CAS  PubMed  Google Scholar 

  43. Divino CM, Chen SH, Yang W, Thung S, Brower ST, Woo SL. Anti-tumor immunity induced by interleukin-12 gene therapy in a metastatic model of breast cancer is mediated by natural killer cells. Breast Cancer Res Treat. 2000;60:129–34.

    Article  CAS  PubMed  Google Scholar 

  44. Lapteva N, Aldrich M, Weksberg D, Rollins L, Goltsova T, Chen SY, et al. Targeting the intratumoral dendritic cells by the oncolytic adenoviral vaccine expressing RANTES elicits potent antitumor immunity. J Immunother. 2009;32:145–56.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Russell SJ, Peng KW, Bell JC. Oncolytic virotherapy. Nat Biotechnol. 2012;30:658–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Greig SL. Talimogene laherparepvec: first global approval. Drugs 2016;76:147–54.

    Article  CAS  PubMed  Google Scholar 

  47. Yamamoto M, Curiel DT. Current issues and future directions of oncolytic adenoviruses. Mol Ther. 2010;18:243–50.

    Article  CAS  PubMed  Google Scholar 

  48. Bauerschmitz GJ, Ranki T, Kangasniemi L, Ribacka C, Eriksson M, Porten M, et al. Tissue-specific promoters active in CD44+CD24-/low breast cancer cells. Cancer Res. 2008;68:5533–9.

    Article  CAS  PubMed  Google Scholar 

  49. Liikanen I, Tahtinen S, Guse K, Gutmann T, Savola P, Oksanen M, et al. Oncolytic adenovirus expressing monoclonal antibody trastuzumab for treatment of HER2-positive cancer. Mol Cancer Ther. 2016;15:2259–69.

    Article  CAS  PubMed  Google Scholar 

  50. Xu W, Yang Y, Hu Z, Head M, Mangold KA, Sullivan M, et al. LyP-1-modified oncolytic adenoviruses targeting transforming growth factor beta inhibit tumor growth and metastases and augment immune checkpoint inhibitor therapy in breast cancer mouse models. Hum Gene Ther. 2020;31:15–6.

  51. Akhtar J, Shukla D. Viral entry mechanisms: cellular and viral mediators of herpes simplex virus entry. FEBS J. 2009;276:7228–36.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Menotti L, Cerretani A, Hengel H, Campadelli-Fiume G. Construction of a fully retargeted herpes simplex virus 1 recombinant capable of entering cells solely via human epidermal growth factor receptor 2. J Virol. 2008;82:10153–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Leoni V, Gatta V, Palladini A, Nicoletti G, Ranieri D, Dall’Ora M, et al. Systemic delivery of HER2-retargeted oncolytic-HSV by mesenchymal stromal cells protects from lung and brain metastases. Oncotarget 2015;6:34774–87.

    Article  PubMed  PubMed Central  Google Scholar 

  54. Ghouse SM, Nguyen HM, Bommareddy PK, Guz-Montgomery K, Saha D. Oncolytic Herpes Simplex virus encoding IL12 controls triple-negative breast cancer growth and metastasis. Front Oncol. 2020;10:384.

    Article  PubMed  PubMed Central  Google Scholar 

  55. Gholami S, Marano A, Chen NG, Aguilar RJ, Frentzen A, Chen CH, et al. A novel vaccinia virus with dual oncolytic and anti-angiogenic therapeutic effects against triple-negative breast cancer. Breast Cancer Res Treat. 2014;148:489–99.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Ferguson MS, Chard Dunmall LS, Gangeswaran R, Marelli G, Tysome JR, Burns E, et al. Transient inhibition of PI3Kdelta enhances the therapeutic effect of intravenous delivery of oncolytic vaccinia virus. Mol Ther. 2020;28:1263–75.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Chon HJ, Lee WS, Yang H, Kong SJ, Lee NK, Moon ES, et al. Tumor microenvironment remodeling by intratumoral oncolytic vaccinia virus enhances the efficacy of immune-checkpoint blockade. Clin Cancer Res. 2019;25:1612–23.

    CAS  PubMed  Google Scholar 

  58. Umer BA, Noyce RS, Franczak BC, Shenouda MM, Kelly RG, Favis NA, et al. Deciphering the immunomodulatory capacity of oncolytic vaccinia virus to enhance the immune response to breast cancer. Cancer Immunol Res. 2020;8:618–31.

    Article  CAS  PubMed  Google Scholar 

  59. Niavarani SR, Lawson C, Boudaud M, Simard C, Tai LH. Oncolytic vesicular stomatitis virus-based cellular vaccine improves triple-negative breast cancer outcome by enhancing natural killer and CD8(+) T-cell functionality. J Immunother Cancer. 2020;8:e000465.

  60. Arulanandam R, Taha Z, Garcia V, Selman M, Chen A, Varette O, et al. The strategic combination of trastuzumab emtansine with oncolytic rhabdoviruses leads to therapeutic synergy. Commun Biol. 2020;3:254.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Bourgeois-Daigneault MC, Roy DG, Aitken AS, El Sayes N, Martin NT, Varette O, et al. Neoadjuvant oncolytic virotherapy before surgery sensitizes triple-negative breast cancer to immune checkpoint therapy. Sci Transl Med. 2018;10:eaao1641.

  62. Bourgeois-Daigneault MC, St-Germain LE, Roy DG, Pelin A, Aitken AS, Arulanandam R, et al. Combination of Paclitaxel and MG1 oncolytic virus as a successful strategy for breast cancer treatment. Breast Cancer Res. 2016;18:83.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  63. Mohamed Amin Z, Che Ani MA, Tan SW, Yeap SK, Alitheen NB, Syed Najmuddin SUF, et al. Evaluation of a recombinant newcastle disease virus expressing human IL12 against human breast cancer. Sci Rep. 2019;9:13999.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  64. Rodriguez Stewart RM, Berry JTL, Berger AK, Yoon SB, Hirsch AL, Guberman JA, et al. Enhanced Killing of Triple-Negative Breast Cancer Cells by Reassortant Reovirus and Topoisomerase Inhibitors. J Virol. 2019;93:e01411-19.

  65. Sahin TT, Kasuya H, Nomura N, Shikano T, Yamamura K, Gewen T, et al. Impact of novel oncolytic virus HF10 on cellular components of the tumor microenviroment in patients with recurrent breast cancer. Cancer Gene Ther. 2012;19:229–37.

    Article  CAS  PubMed  Google Scholar 

  66. Bernstein V, Ellard SL, Dent SF, Tu D, Mates M, Dhesy-Thind SK, et al. A randomized phase II study of weekly paclitaxel with or without pelareorep in patients with metastatic breast cancer: final analysis of Canadian Cancer Trials Group IND.213. Breast Cancer Res Treat. 2018;167:485–93.

    Article  CAS  PubMed  Google Scholar 

  67. Parato KA, Senger D, Forsyth PA, Bell JC. Recent progress in the battle between oncolytic viruses and tumours. Nat Rev Cancer. 2005;5:965–76.

    Article  CAS  PubMed  Google Scholar 

  68. Filley AC, Dey M. Immune system, friend or foe of oncolytic virotherapy? Front Oncol. 2017;7:106.

    Article  PubMed  PubMed Central  Google Scholar 

  69. Atezolizumab for the treatment of breast cancer. PMID: 32067545.

  70. Wakimoto H, Fulci G, Tyminski E, Chiocca EA. Altered expression of antiviral cytokine mRNAs associated with cyclophosphamide’s enhancement of viral oncolysis. Gene Ther. 2004;11:214–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Fulci G, Breymann L, Gianni D, Kurozomi K, Rhee SS, Yu J, et al. Cyclophosphamide enhances glioma virotherapy by inhibiting innate immune responses. Proc Natl Acad Sci USA. 2006;103:12873–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Prestwich RJ, Ilett EJ, Errington F, Diaz RM, Steele LP, Kottke T, et al. Immune-mediated antitumor activity of reovirus is required for therapy and is independent of direct viral oncolysis and replication. Clin Cancer Res. 2009;15:4374–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Apostolidis L, Schirrmacher V, Fournier P. Host mediated anti-tumor effect of oncolytic Newcastle disease virus after locoregional application. Int J Oncol. 2007;31:1009–19.

    CAS  PubMed  Google Scholar 

  74. Kleijn A, Kloezeman J, Treffers-Westerlaken E, Fulci G, Leenstra S, Dirven C, et al. The therapeutic efficacy of the oncolytic virus Delta24-RGD in a murine glioma model depends primarily on antitumor immunity. Oncoimmunology 2014;3:e955697.

    Article  PubMed  PubMed Central  Google Scholar 

  75. Leddon JL, Chen CY, Currier MA, Wang PY, Jung FA, Denton NL, et al. Oncolytic HSV virotherapy in murine sarcomas differentially triggers an antitumor T-cell response in the absence of virus permissivity. Mol Ther Oncolytics. 2015;1:14010.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  76. Bridle BW, Clouthier D, Zhang L, Pol J, Chen L, Lichty BD, et al. Oncolytic vesicular stomatitis virus quantitatively and qualitatively improves primary CD8(+) T-cell responses to anticancer vaccines. Oncoimmunology. 2013;2:e26013.

    Article  PubMed  PubMed Central  Google Scholar 

  77. Li H, Dutuor A, Fu X, Zhang X. Induction of strong antitumor immunity by an HSV-2-based oncolytic virus in a murine mammary tumor model. J Gene Med. 2007;9:161–9.

    Article  CAS  PubMed  Google Scholar 

  78. Miller CG, Fraser NW. Requirement of an integrated immune response for successful neuroattenuated HSV-1 therapy in an intracranial metastatic melanoma model. Mol Ther. 2003;7:741–7.

    Article  CAS  PubMed  Google Scholar 

  79. Qiao J, Kottke T, Willmon C, Galivo F, Wongthida P, Diaz RM, et al. Purging metastases in lymphoid organs using a combination of antigen-nonspecific adoptive T cell therapy, oncolytic virotherapy and immunotherapy. Nat Med. 2008;14:37–44.

    Article  CAS  PubMed  Google Scholar 

  80. Gujar S, Pol JG, Kim Y, Lee PW, Kroemer G. Antitumor benefits of antiviral immunity: an underappreciated aspect of oncolytic virotherapies. Trends Immunol. 2018;39:209–21.

    Article  CAS  PubMed  Google Scholar 

  81. Dai P, Wang W, Yang N, Serna-Tamayo C, Ricca JM, Zamarin D, et al. Intratumoral delivery of inactivated modified vaccinia virus Ankara (iMVA) induces systemic antitumor immunity via STING and Batf3-dependent dendritic cells. Sci Immunol. 2017;2:eaal1713.

  82. Guo ZS, Liu Z, Bartlett DL. Oncolytic immunotherapy: dying the right way is a key to eliciting potent antitumor immunity. Front Oncol. 2014;4:74.

    PubMed  PubMed Central  Google Scholar 

  83. Chaurasiya S, Chen NG, Fong Y. Oncolytic viruses and immunity. Curr Opin Immunol. 2018;51:83–90.

    Article  CAS  PubMed  Google Scholar 

  84. Tang D, Kang R, Coyne CB, Zeh HJ, Lotze MT. PAMPs and DAMPs: signal 0s that spur autophagy and immunity. Immunol Rev. 2012;249:158–75.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Ribas A, Dummer R, Puzanov I, VanderWalde A, Andtbacka RHI, Michielin O, et al. Oncolytic virotherapy promotes intratumoral T cell infiltration and improves anti-PD-1 immunotherapy. Cell 2017;170:1109–19.e10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Gujar S, Pol JG, Kroemer G. Heating it up: oncolytic viruses make tumors ‘hot’ and suitable for checkpoint blockade immunotherapies. Oncoimmunology. 2018;7:e1442169.

    Article  PubMed  PubMed Central  Google Scholar 

  87. Chaurasiya S, Yang A, Kang S, Lu J, Kim SI, Park AK, et al. Oncolytic poxvirus CF33-hNIS-DeltaF14.5 favorably modulates tumor immune microenvironment and works synergistically with anti-PD-L1 antibody in a triple-negative breast cancer model. Oncoimmunology. 2020;9:1729300.

    Article  PubMed  PubMed Central  Google Scholar 

  88. Mostafa AA, Meyers DE, Thirukkumaran CM, Liu PJ, Gratton K, Spurrell J, et al. Oncolytic reovirus and immune checkpoint inhibition as a novel immunotherapeutic strategy for breast cancer. Cancers. 2018;10:205.

  89. Workenhe ST, Mossman KL. Oncolytic virotherapy and immunogenic cancer cell death: sharpening the sword for improved cancer treatment strategies. Mol Ther. 2014;22:251–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Kroemer G, Galluzzi L, Kepp O, Zitvogel L. Immunogenic cell death in cancer therapy. Annu Rev Immunol. 2013;31:51–72.

    Article  CAS  PubMed  Google Scholar 

  91. Martin NT, Roy DG, Workenhe ST, van den Wollenberg DJM, Hoeben RC, Mossman KL, et al. Pre-surgical neoadjuvant oncolytic virotherapy confers protection against rechallenge in a murine model of breast cancer. Sci Rep. 2019;9:1865.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  92. Zhu W, Wei L, Zhang H, Chen J, Qin X. Oncolytic adenovirus armed with IL-24 inhibits the growth of breast cancer in vitro and in vivo. J Exp Clin Cancer Res. 2012;31:51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Bramante S, Koski A, Liikanen I, Vassilev L, Oksanen M, Siurala M, et al. Oncolytic virotherapy for treatment of breast cancer, including triple-negative breast cancer. Oncoimmunology. 2016;5:e1078057.

    Article  PubMed  CAS  Google Scholar 

  94. Liu Z, Ravindranathan R, Kalinski P, Guo ZS, Bartlett DL. Rational combination of oncolytic vaccinia virus and PD-L1 blockade works synergistically to enhance therapeutic efficacy. Nat Commun. 2017;8:14754.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Chaurasiya S, Fong Y, Warner SG. Optimizing oncolytic viral design to enhance antitumor efficacy: progress and challenges. Cancers. 2020;12:1699.

  96. Choi AH, O’Leary MP, Lu J, Kim SI, Fong Y, Chen NG. Endogenous Akt activity promotes virus entry and predicts efficacy of novel chimeric orthopoxvirus in triple-negative breast cancer. Mol Ther Oncolytics. 2018;9:22–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Ricordel M, Foloppe J, Antoine D, Findeli A, Kempf J, Cordier P, et al. Vaccinia virus shuffling: deVV5, a novel chimeric poxvirus with improved oncolytic potency. Cancers. 2018;10:231.

  98. Breitbach CJ, Burke J, Jonker D, Stephenson J, Haas AR, Chow LQ, et al. Intravenous delivery of a multi-mechanistic cancer-targeted oncolytic poxvirus in humans. Nature 2011;477:99–102.

    Article  CAS  PubMed  Google Scholar 

  99. Wojton J, Kaur B. Impact of tumor microenvironment on oncolytic viral therapy. Cytokine Growth Factor Rev. 2010;21:127–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Martinez-Quintanilla J, Seah I, Chua M, Shah K. Oncolytic viruses: overcoming translational challenges. J Clin Invest. 2019;130:1407–18.

    Article  Google Scholar 

  101. McGray AJR, Huang RY, Battaglia S, Eppolito C, Miliotto A, Stephenson KB, et al. Oncolytic Maraba virus armed with tumor antigen boosts vaccine priming and reveals diverse therapeutic response patterns when combined with checkpoint blockade in ovarian cancer. J Immunother Cancer. 2019;7:189.

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

Shyambabu Chaurasiya is supported through the generosity of the Natalie and David Roberts Family. We wish to thank them for their philanthropy.

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Chaurasiya, S., Fong, Y. Viroimmunotherapy for breast cancer: promises, problems and future directions. Cancer Gene Ther 28, 757–768 (2021). https://doi.org/10.1038/s41417-020-00265-6

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