Systemic Delivery of Oncolytic Viruses: Hopes and Hurdles
TLDR
The potential advantages of, and obstacles to, successful systemic delivery of oncolytic viruses are discussed and a range of methods have been reported in the literature, which are designed to overcome these hurdles in preclinical models.Abstract:
Despite recent advances in both surgery and chemoradiotherapy, mortality rates for advanced cancer remain high. There is a pressing need for novel therapeutic strategies; one option is systemic oncolytic viral therapy. Intravenous administration affords the opportunity to treat both the primary tumour and any metastatic deposits simultaneously. Data from clinical trials have shown that oncolytic viruses can be systemically delivered safely with limited toxicity but the results are equivocal in terms of efficacy, particularly when delivered with adjuvant chemotherapy. A key reason for this is the rapid clearance of the viruses from the circulation before they reach their targets. This phenomenon is mainly mediated through neutralising antibodies, complement activation, antiviral cytokines, and tissue-resident macrophages, as well as nonspecific uptake by other tissues such as the lung, liver and spleen, and suboptimal viral escape from the vascular compartment. A range of methods have been reported in the literature, which are designed to overcome these hurdles in preclinical models. In this paper, the potential advantages of, and obstacles to, successful systemic delivery of oncolytic viruses are discussed. The next stage of development will be the commencement of clinical trials combining these novel approaches for overcoming the barriers with systemically delivered oncolytic viruses.read more
Citations
More filters
Journal ArticleDOI
Integrating oncolytic viruses in combination cancer immunotherapy
TL;DR: Oncolytic viruses can target multiple steps in the cancer–immunity cycle and can be engineered to express therapeutic genes and, as a result, can be usefully integrated in combination cancer immunotherapies.
Journal ArticleDOI
Optimizing oncolytic virotherapy in cancer treatment.
Kevin J. Harrington,Daniel J. Freeman,Beth Kelly,James Harper,Jean-Charles Soria,Jean-Charles Soria +5 more
TL;DR: Rational combinations of OVs with different immune modifiers and/or antitumour agents, based on mechanisms of tumour resistance to immune-mediated attack, may benefit the large, currently underserved, population of patients who respond poorly to immune checkpoint inhibition.
Journal ArticleDOI
Trial watch: Oncolytic viruses for cancer therapy
Erika Vacchelli,Alexander M.M. Eggermont,Catherine Sautès-Fridman,Jérôme Galon,Laurence Zitvogel,Guido Kroemer,Lorenzo Galluzzi +6 more
TL;DR: The latest advances in this active area of translational investigation are covered, summarizing high-impact studies that have been published during the last 12 months and discussing clinical trials that have be initiated in the same period to assess the therapeutic potential of oncolytic virotherapy in oncological indications.
Journal ArticleDOI
Harnessing the immune system to improve cancer therapy.
Nikos E. Papaioannou,Ourania V. Beniata,Panagiotis Vitsos,Ourania E. Tsitsilonis,Pinelopi Samara +4 more
TL;DR: The most popular cancer immunotherapy approaches are presented and their clinical relevance is discussed referring to data acquired from clinical trials.
Journal ArticleDOI
Oncolytic Viral Therapy and the Immune System: A Double-Edged Sword Against Cancer.
TL;DR: The different immune responses are analyzed in order to highlight the new and promising perspectives leading to increased anti-tumor response and decreased immune reaction to the OVs.
References
More filters
Journal ArticleDOI
Antiviral Actions of Interferons
TL;DR: Tremendous progress has been made in understanding the molecular basis of the antiviral actions of interferons (IFNs), as well as strategies evolved by viruses to antagonize the actions of IFNs.
Journal ArticleDOI
IFN-lambdas mediate antiviral protection through a distinct class II cytokine receptor complex.
Sergei V. Kotenko,Grant Gallagher,Vitaliy V. Baurin,Anita Lewis-Antes,Meiling Shen,Nital K. Shah,Jerome A. Langer,Faruk Sheikh,Harold Dickensheets,Raymond P. Donnelly +9 more
TL;DR: The identification of a ligand-receptor system that, upon engagement, leads to the establishment of an antiviral state and may contribute to antiviral or other defenses by a mechanism similar to, but independent of, type I IFNs.
Journal ArticleDOI
Interferons and viruses: an interplay between induction, signalling, antiviral responses and virus countermeasures.
TL;DR: Applied aspects that arise from an increase in knowledge in this area are described, including vaccine design and manufacture, the development of novel antiviral drugs and the use of IFN-sensitive oncolytic viruses in the treatment of cancer.
Journal ArticleDOI
A controlled trial of intratumoral ONYX-015, a selectively-replicating adenovirus, in combination with cisplatin and 5-fluorouracil in patients with recurrent head and neck cancer
Fadlo R. Khuri,John Nemunaitis,Ian Ganly,James Arseneau,Ian F. Tannock,Larry Romel,Martin Gore,J. Ironside,Robert Hugh MacDougall,Carla Heise,Britta Randlev,Ann M. Gillenwater,Patricia A. Bruso,Stanley B. Kaye,Waun Ki Hong,David H. Kirn +15 more
TL;DR: A phase II trial of a combination of intratumoral ONYX-015 injection with cisplatin and 5-fluorouracil in patients with recurrent squamous cell cancer of the head and neck found substantial objective responses, including a high proportion of complete responses.
Journal ArticleDOI
Type I Interferons in Host Defense
TL;DR: Advances highlight the context-specific actions of type I IFNs and clarify the multiple points at which they are integrated into both innate and adaptive immunity.
Related Papers (5)
Talimogene Laherparepvec Improves Durable Response Rate in Patients With Advanced Melanoma
Robert H.I. Andtbacka,Howard L. Kaufman,Frances A. Collichio,Thomas Amatruda,Neil Senzer,Jason Chesney,Keith A. Delman,Lynn E. Spitler,Igor Puzanov,Sanjiv S. Agarwala,Mohammed M. Milhem,Lee D. Cranmer,Brendan D. Curti,Karl D. Lewis,Merrick I. Ross,Troy H. Guthrie,Gerald P. Linette,Gregory A. Daniels,Kevin J. Harrington,Mark R. Middleton,Wilson H. Miller,Jonathan S. Zager,Yining Ye,Bin Yao,Ai Li,Susan Doleman,Ari M. Vanderwalde,Jennifer Gansert,Robert Coffin +28 more
Randomized dose-finding clinical trial of oncolytic immunotherapeutic vaccinia JX-594 in liver cancer
Jeong Heo,Tony R. Reid,Leyo Ruo,Caroline J. Breitbach,Steven C. Rose,Mark Bloomston,Mong Cho,Ho Yeong Lim,Hyun Cheol Chung,Chang Won Kim,James M. Burke,Riccardo Lencioni,Theresa Hickman,Anne Moon,Yeon Sook Lee,Mi Kyeong Kim,Manijeh Daneshmand,Kara S DuBois,Lara Longpre,Minhtran C. Ngo,Cliona M. Rooney,John C. Bell,Byung Geon Rhee,Richard H. Patt,Tae-Ho Hwang,David H. Kirn +25 more
Oncolytic Virotherapy Promotes Intratumoral T Cell Infiltration and Improves Anti-PD-1 Immunotherapy
Antoni Ribas,Reinhard Dummer,Igor Puzanov,Ari M. Vanderwalde,Robert H.I. Andtbacka,Olivier Michielin,Anthony J. Olszanski,Josep Malvehy,Jonathan Cebon,Eugenio Fernandez,John M. Kirkwood,Thomas F. Gajewski,Lisa Chen,Kevin S. Gorski,Abraham Anderson,Scott J. Diede,Michael E. Lassman,Jennifer Gansert,F. Stephen Hodi,Georgina V. Long +19 more