Vaccinia virus-mediated cancer immunotherapy: cancer vaccines and oncolytics

Cancer vaccines and oncolytic immunotherapy are promising treatment strategies with potential to provide greater clinical benefit to patients with advanced-stage cancer. In particular, recombinant vaccinia viruses (VV) hold great promise as interventional agents. In this article, we first summarize...

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Published inJournal for immunotherapy of cancer Vol. 7; no. 1; p. 6
Main Authors Guo, Zong Sheng, Lu, Binfeng, Guo, Zongbi, Giehl, Esther, Feist, Mathilde, Dai, Enyong, Liu, Weilin, Storkus, Walter J, He, Yukai, Liu, Zuqiang, Bartlett, David L
Format Journal Article
LanguageEnglish
Published England BioMed Central Ltd 09.01.2019
BMJ Publishing Group LTD
BioMed Central
BMJ Publishing Group
Subjects
Animals
Breast cancer
Cancer
Cancer vaccines
Cancer Vaccines - administration & dosage
Cancer Vaccines - genetics
Cancer Vaccines - immunology
Care and treatment
Clinical Studies as Topic
Dendritic Cells - immunology
Dendritic Cells - metabolism
Genetic Engineering
Genetic Therapy
Genetic Vectors - administration & dosage
Genetic Vectors - genetics
Host-Pathogen Interactions - immunology
Humans
Immunotherapy
Kinases
Membrane Glycoproteins - administration & dosage
Membrane Glycoproteins - immunology
Neoplasms - genetics
Neoplasms - immunology
Neoplasms - therapy
Oncolytic Virotherapy
Oncolytic Viruses - genetics
Oncolytic Viruses - physiology
Review
T-Lymphocytes - immunology
T-Lymphocytes - metabolism
Transcription factors
Vaccines
Vaccinia
Vaccinia virus - genetics
Vaccinia virus - physiology
Viral infections
Viruses
Online AccessGet full text

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Abstract Cancer vaccines and oncolytic immunotherapy are promising treatment strategies with potential to provide greater clinical benefit to patients with advanced-stage cancer. In particular, recombinant vaccinia viruses (VV) hold great promise as interventional agents. In this article, we first summarize the current understanding of virus biology and viral genes involved in host-virus interactions to further improve the utility of these agents in therapeutic applications. We then discuss recent findings from basic and clinical studies using VV as cancer vaccines and oncolytic immunotherapies. Despite encouraging results gleaned from translational studies in animal models, clinical trials implementing VV vectors alone as cancer vaccines have yielded largely disappointing results. However, the combination of VV vaccines with alternate forms of standard therapies has resulted in superior clinical efficacy. For instance, combination regimens using TG4010 (MVA-MUC1-IL2) with first-line chemotherapy in advanced-stage non-small cell lung cancer or combining PANVAC with docetaxel in the setting of metastatic breast cancer have clearly provided enhanced clinical benefits to patients. Another novel cancer vaccine approach is to stimulate anti-tumor immunity via STING activation in Batf3-dependent dendritic cells (DC) through the use of replication-attenuated VV vectors. Oncolytic VVs have now been engineered for improved safety and superior therapeutic efficacy by arming them with immune-stimulatory genes or pro-apoptotic molecules to facilitate tumor immunogenic cell death, leading to enhanced DC-mediated cross-priming of T cells recognizing tumor antigens, including neoantigens. Encouraging translational and early phase clinical results with Pexa-Vec have matured into an ongoing global phase III trial for patients with hepatocellular carcinoma. Combinatorial approaches, most notably those using immune checkpoint blockade, have produced exciting pre-clinical results and warrant the development of innovative clinical studies. Finally, we discuss major hurdles that remain in the field and offer some perspectives regarding the development of next generation VV vectors for use as cancer therapeutics.
AbstractList Cancer vaccines and oncolytic immunotherapy are promising treatment strategies with potential to provide greater clinical benefit to patients with advanced-stage cancer. In particular, recombinant vaccinia viruses (VV) hold great promise as interventional agents. In this article, we first summarize the current understanding of virus biology and viral genes involved in host-virus interactions to further improve the utility of these agents in therapeutic applications. We then discuss recent findings from basic and clinical studies using VV as cancer vaccines and oncolytic immunotherapies. Despite encouraging results gleaned from translational studies in animal models, clinical trials implementing VV vectors alone as cancer vaccines have yielded largely disappointing results. However, the combination of VV vaccines with alternate forms of standard therapies has resulted in superior clinical efficacy. For instance, combination regimens using TG4010 (MVA-MUC1-IL2) with first-line chemotherapy in advanced-stage non-small cell lung cancer or combining PANVAC with docetaxel in the setting of metastatic breast cancer have clearly provided enhanced clinical benefits to patients. Another novel cancer vaccine approach is to stimulate anti-tumor immunity via STING activation in Batf3-dependent dendritic cells (DC) through the use of replication-attenuated VV vectors. Oncolytic VVs have now been engineered for improved safety and superior therapeutic efficacy by arming them with immune-stimulatory genes or pro-apoptotic molecules to facilitate tumor immunogenic cell death, leading to enhanced DC-mediated cross-priming of T cells recognizing tumor antigens, including neoantigens. Encouraging translational and early phase clinical results with Pexa-Vec have matured into an ongoing global phase III trial for patients with hepatocellular carcinoma. Combinatorial approaches, most notably those using immune checkpoint blockade, have produced exciting pre-clinical results and warrant the development of innovative clinical studies. Finally, we discuss major hurdles that remain in the field and offer some perspectives regarding the development of next generation VV vectors for use as cancer therapeutics.
Abstract Cancer vaccines and oncolytic immunotherapy are promising treatment strategies with potential to provide greater clinical benefit to patients with advanced-stage cancer. In particular, recombinant vaccinia viruses (VV) hold great promise as interventional agents. In this article, we first summarize the current understanding of virus biology and viral genes involved in host-virus interactions to further improve the utility of these agents in therapeutic applications. We then discuss recent findings from basic and clinical studies using VV as cancer vaccines and oncolytic immunotherapies. Despite encouraging results gleaned from translational studies in animal models, clinical trials implementing VV vectors alone as cancer vaccines have yielded largely disappointing results. However, the combination of VV vaccines with alternate forms of standard therapies has resulted in superior clinical efficacy. For instance, combination regimens using TG4010 (MVA-MUC1-IL2) with first-line chemotherapy in advanced-stage non-small cell lung cancer or combining PANVAC with docetaxel in the setting of metastatic breast cancer have clearly provided enhanced clinical benefits to patients. Another novel cancer vaccine approach is to stimulate anti-tumor immunity via STING activation in Batf3-dependent dendritic cells (DC) through the use of replication-attenuated VV vectors. Oncolytic VVs have now been engineered for improved safety and superior therapeutic efficacy by arming them with immune-stimulatory genes or pro-apoptotic molecules to facilitate tumor immunogenic cell death, leading to enhanced DC-mediated cross-priming of T cells recognizing tumor antigens, including neoantigens. Encouraging translational and early phase clinical results with Pexa-Vec have matured into an ongoing global phase III trial for patients with hepatocellular carcinoma. Combinatorial approaches, most notably those using immune checkpoint blockade, have produced exciting pre-clinical results and warrant the development of innovative clinical studies. Finally, we discuss major hurdles that remain in the field and offer some perspectives regarding the development of next generation VV vectors for use as cancer therapeutics.
ArticleNumber 6
Audience Academic
Author Storkus, Walter J
Bartlett, David L
Guo, Zongbi
Lu, Binfeng
He, Yukai
Feist, Mathilde
Guo, Zong Sheng
Giehl, Esther
Dai, Enyong
Liu, Weilin
Liu, Zuqiang
Author_xml – sequence: 1
  givenname: Zong Sheng
  orcidid: 0000-0002-4624-9907
  surname: Guo
  fullname: Guo, Zong Sheng
  email: guozs@upmc.edu, guozs@upmc.edu
  organization: Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. guozs@upmc.edu
– sequence: 2
  givenname: Binfeng
  surname: Lu
  fullname: Lu, Binfeng
  organization: Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
– sequence: 3
  givenname: Zongbi
  surname: Guo
  fullname: Guo, Zongbi
  organization: Fujian Tianjian Pharmaceutical Co. Ltd., Sanming, Fujian, China
– sequence: 4
  givenname: Esther
  surname: Giehl
  fullname: Giehl, Esther
  organization: Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
– sequence: 5
  givenname: Mathilde
  surname: Feist
  fullname: Feist, Mathilde
  organization: Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
– sequence: 6
  givenname: Enyong
  surname: Dai
  fullname: Dai, Enyong
  organization: Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
– sequence: 7
  givenname: Weilin
  surname: Liu
  fullname: Liu, Weilin
  organization: Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
– sequence: 8
  givenname: Walter J
  surname: Storkus
  fullname: Storkus, Walter J
  organization: Department of Dermatology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
– sequence: 9
  givenname: Yukai
  surname: He
  fullname: He, Yukai
  organization: Georgia Cancer Center, Medical College of Georgia, Augusta University, Augusta, GA, USA
– sequence: 10
  givenname: Zuqiang
  surname: Liu
  fullname: Liu, Zuqiang
  organization: Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
– sequence: 11
  givenname: David L
  surname: Bartlett
  fullname: Bartlett, David L
  organization: Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
BackLink https://www.ncbi.nlm.nih.gov/pubmed/30626434$$D View this record in MEDLINE/PubMed
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SecondaryResourceType review_article
Snippet Cancer vaccines and oncolytic immunotherapy are promising treatment strategies with potential to provide greater clinical benefit to patients with...
Abstract Cancer vaccines and oncolytic immunotherapy are promising treatment strategies with potential to provide greater clinical benefit to patients with...
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pubmedcentral
proquest
gale
crossref
pubmed
SourceType Open Website
Open Access Repository
Aggregation Database
Index Database
StartPage 6
SubjectTerms Animals
Breast cancer
Cancer
Cancer vaccines
Cancer Vaccines - administration & dosage
Cancer Vaccines - genetics
Cancer Vaccines - immunology
Care and treatment
Clinical Studies as Topic
Dendritic Cells - immunology
Dendritic Cells - metabolism
Genetic Engineering
Genetic Therapy
Genetic Vectors - administration & dosage
Genetic Vectors - genetics
Host-Pathogen Interactions - immunology
Humans
Immunotherapy
Kinases
Membrane Glycoproteins - administration & dosage
Membrane Glycoproteins - immunology
Neoplasms - genetics
Neoplasms - immunology
Neoplasms - therapy
Oncolytic Virotherapy
Oncolytic Viruses - genetics
Oncolytic Viruses - physiology
Review
T-Lymphocytes - immunology
T-Lymphocytes - metabolism
Transcription factors
Vaccines
Vaccinia
Vaccinia virus - genetics
Vaccinia virus - physiology
Viral infections
Viruses
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Title Vaccinia virus-mediated cancer immunotherapy: cancer vaccines and oncolytics
URI https://www.ncbi.nlm.nih.gov/pubmed/30626434
https://www.proquest.com/docview/2638110852
https://search.proquest.com/docview/2179318657
https://pubmed.ncbi.nlm.nih.gov/PMC6325819
https://doaj.org/article/dd58871640dd4377a7310da801381607
Volume 7
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