Oncolytic Immunotherapy: Conceptual Evolution, Current Strategies, and Future Perspectives
The concept of oncolytic virus (OV)-mediated cancer therapy has been shifted from an operational virotherapy paradigm to an immunotherapy. OVs often induce immunogenic cell death (ICD) of cancer cells, and they may interact directly with immune cells as well to prime antitumor immunity. We and other...
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doaj-7a01c40d34e143c4b2b96651a746794f2020-11-24T22:43:33ZengFrontiers Media S.A.Frontiers in Immunology1664-32242017-05-01810.3389/fimmu.2017.00555261904Oncolytic Immunotherapy: Conceptual Evolution, Current Strategies, and Future PerspectivesZong Sheng Guo0Zong Sheng Guo1Zuqiang Liu2Zuqiang Liu3Stacy Kowalsky4Stacy Kowalsky5Mathilde Feist6Mathilde Feist7Mathilde Feist8Pawel Kalinski9Pawel Kalinski10Pawel Kalinski11Binfeng Lu12Binfeng Lu13Walter J. Storkus14Walter J. Storkus15Walter J. Storkus16David L. Bartlett17David L. Bartlett18University of Pittsburgh Cancer Institute, Pittsburgh, PA, USADepartment of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USAUniversity of Pittsburgh Cancer Institute, Pittsburgh, PA, USADepartment of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USAUniversity of Pittsburgh Cancer Institute, Pittsburgh, PA, USADepartment of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USAUniversity of Pittsburgh Cancer Institute, Pittsburgh, PA, USADepartment of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USADepartment of Surgery, CCM/CVK, Charité – Universitaetsmedizin Berlin, Berlin, GermanyUniversity of Pittsburgh Cancer Institute, Pittsburgh, PA, USADepartment of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USADepartment of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USAUniversity of Pittsburgh Cancer Institute, Pittsburgh, PA, USADepartment of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USAUniversity of Pittsburgh Cancer Institute, Pittsburgh, PA, USADepartment of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USADepartment of Dermatology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USAUniversity of Pittsburgh Cancer Institute, Pittsburgh, PA, USADepartment of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USAThe concept of oncolytic virus (OV)-mediated cancer therapy has been shifted from an operational virotherapy paradigm to an immunotherapy. OVs often induce immunogenic cell death (ICD) of cancer cells, and they may interact directly with immune cells as well to prime antitumor immunity. We and others have developed a number of strategies to further stimulate antitumor immunity and to productively modulate the tumor microenvironment (TME) for potent and sustained antitumor immune cell activity. First, OVs have been engineered or combined with other ICD inducers to promote more effective T cell cross-priming, and in many cases, the breaking of functional immune tolerance. Second, OVs may be armed to express Th1-stimulatory cytokines/chemokines or costimulators to recruit and sustain the potent antitumor immunity into the TME to focus their therapeutic activity within the sites of disease. Third, combinations of OV with immunomodulatory drugs or antibodies that recondition the TME have proven to be highly promising in early studies. Fourth, combinations of OVs with other immunotherapeutic regimens (such as prime-boost cancer vaccines, CAR T cells; armed with bispecific T-cell engagers) have also yielded promising preliminary findings. Finally, OVs have been combined with immune checkpoint blockade, with robust antitumor efficacy being observed in pilot evaluations. Despite some expected hurdles for the rapid translation of OV-based state-of-the-art protocols, we believe that a cohort of these novel approaches will join the repertoire of standard cancer treatment options in the near future.http://journal.frontiersin.org/article/10.3389/fimmu.2017.00555/fullimmunogenic cell deathICD inducerantigencross-presentationimmune checkpoint blockadeantitumor immunity |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Zong Sheng Guo Zong Sheng Guo Zuqiang Liu Zuqiang Liu Stacy Kowalsky Stacy Kowalsky Mathilde Feist Mathilde Feist Mathilde Feist Pawel Kalinski Pawel Kalinski Pawel Kalinski Binfeng Lu Binfeng Lu Walter J. Storkus Walter J. Storkus Walter J. Storkus David L. Bartlett David L. Bartlett |
spellingShingle |
Zong Sheng Guo Zong Sheng Guo Zuqiang Liu Zuqiang Liu Stacy Kowalsky Stacy Kowalsky Mathilde Feist Mathilde Feist Mathilde Feist Pawel Kalinski Pawel Kalinski Pawel Kalinski Binfeng Lu Binfeng Lu Walter J. Storkus Walter J. Storkus Walter J. Storkus David L. Bartlett David L. Bartlett Oncolytic Immunotherapy: Conceptual Evolution, Current Strategies, and Future Perspectives Frontiers in Immunology immunogenic cell death ICD inducer antigen cross-presentation immune checkpoint blockade antitumor immunity |
author_facet |
Zong Sheng Guo Zong Sheng Guo Zuqiang Liu Zuqiang Liu Stacy Kowalsky Stacy Kowalsky Mathilde Feist Mathilde Feist Mathilde Feist Pawel Kalinski Pawel Kalinski Pawel Kalinski Binfeng Lu Binfeng Lu Walter J. Storkus Walter J. Storkus Walter J. Storkus David L. Bartlett David L. Bartlett |
author_sort |
Zong Sheng Guo |
title |
Oncolytic Immunotherapy: Conceptual Evolution, Current Strategies, and Future Perspectives |
title_short |
Oncolytic Immunotherapy: Conceptual Evolution, Current Strategies, and Future Perspectives |
title_full |
Oncolytic Immunotherapy: Conceptual Evolution, Current Strategies, and Future Perspectives |
title_fullStr |
Oncolytic Immunotherapy: Conceptual Evolution, Current Strategies, and Future Perspectives |
title_full_unstemmed |
Oncolytic Immunotherapy: Conceptual Evolution, Current Strategies, and Future Perspectives |
title_sort |
oncolytic immunotherapy: conceptual evolution, current strategies, and future perspectives |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Immunology |
issn |
1664-3224 |
publishDate |
2017-05-01 |
description |
The concept of oncolytic virus (OV)-mediated cancer therapy has been shifted from an operational virotherapy paradigm to an immunotherapy. OVs often induce immunogenic cell death (ICD) of cancer cells, and they may interact directly with immune cells as well to prime antitumor immunity. We and others have developed a number of strategies to further stimulate antitumor immunity and to productively modulate the tumor microenvironment (TME) for potent and sustained antitumor immune cell activity. First, OVs have been engineered or combined with other ICD inducers to promote more effective T cell cross-priming, and in many cases, the breaking of functional immune tolerance. Second, OVs may be armed to express Th1-stimulatory cytokines/chemokines or costimulators to recruit and sustain the potent antitumor immunity into the TME to focus their therapeutic activity within the sites of disease. Third, combinations of OV with immunomodulatory drugs or antibodies that recondition the TME have proven to be highly promising in early studies. Fourth, combinations of OVs with other immunotherapeutic regimens (such as prime-boost cancer vaccines, CAR T cells; armed with bispecific T-cell engagers) have also yielded promising preliminary findings. Finally, OVs have been combined with immune checkpoint blockade, with robust antitumor efficacy being observed in pilot evaluations. Despite some expected hurdles for the rapid translation of OV-based state-of-the-art protocols, we believe that a cohort of these novel approaches will join the repertoire of standard cancer treatment options in the near future. |
topic |
immunogenic cell death ICD inducer antigen cross-presentation immune checkpoint blockade antitumor immunity |
url |
http://journal.frontiersin.org/article/10.3389/fimmu.2017.00555/full |
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