Use of an oncolytic virus secreting GM-CSF as combined oncolytic and immunotherapy for treatment of colorectal and hepatic adenocarcinomas

Malhotra, Sandeep K.; Kim, Teresa S.; Zager, Jonathan S.; Bennett, Joseph; Ebright, Michael I.; D’Angelica, Michael I.; Fong, Yuman

doi:10.1016/j.surg.2006.10.010

Cited by 71 publications

(58 citation statements)

References 33 publications

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“…Oncolytic viruses engineered to secrete GM-CSF have been reported to show higher antitumor activity (13). Co-injection of GM-CSF-expressing virus also enhanced the anticancer effect of oncolytic viruses (14).…”

Section: Discussionmentioning

confidence: 99%

Oncolytic plasmid: A novel strategy for tumor immuno-gene therapy

et al. 2011

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Abstract. The oncolytic virus is expected to proliferate in and destroy tumor cells. The virus is also thought to generate antitumor immunity. Virally infected tumor cells express viral antigens on their surfaces. Such tumor cells or their fragments would be taken up by antigen-presenting cells (APCs) together with tumor-associated antigens (TAAs), and facilitated cross-priming of tumor-specific T cells. Virus-specific protein presented on the infected cells therefore played a crucial role in the enhancement of the adaptive antitumor immunity. In this study, a plasmid encoding adenovirus protein, the adenovirus death protein (ADP), was constructed, and a very fine complex of the plasmid with polyethylenimine (PEI) and chondroitin sulfate (CS) was injected into tumor-bearing mice. Transfection of the ADP gene was shown to suppress tumor growth as effectively as granulocyte-macrophage colonystimulating factor (GM-CSF) transfection. When mice were administered plasmid coding ADP (pDNA-ADP) to generate an immune response to ADP prior to therapy, transfection of the ADP gene induced a much higher level of tumor growth suppression than that found in the non-immunized mice. An evident synergistic effect of ADP and GM-CSF genes was also observed, and at a pDNA-ADP/pDNA-GM-CSF ratio of 4:1, significant suppression of tumor growth was achieved even in the non-immunized mice.

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Section: Discussionmentioning

confidence: 99%

Oncolytic plasmid: A novel strategy for tumor immuno-gene therapy

et al. 2011

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“…In an abiotic context, adaptive capacity can also be determined by features such as high river connectivity (Khamis et al, 2013), stable hydrological cycles (Thomas, 2016), and heterogeneous landscape (Czucz et al, 2011). A second approach is to raise social and institutional capabilities, such as accessibility to information and resources (Milman and Short, 2008), responsiveness to environmental change (Malhotra et al, 2007), enhanced institutional structure and governance processes da Silveira and Richards, 2013), boosted stakeholder participation (Few et al, 2007), and encouragement of learning and knowledge dissemination and exchange (Pahl-Wostl, 2009). …”

Section: Building Pathways To Resilience In Socio-hydrological Contextsmentioning

confidence: 99%

HESS Opinions: A conceptual framework for assessing socio-hydrological resilience under change

Mao

Clark

Karpouzoglou

et al. 2017

Hydrol. Earth Syst. Sci.

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Abstract. Despite growing interest in resilience, there is still significant scope for increasing its conceptual clarity and practical relevance in socio-hydrological contexts: specifically, questions of how socio-hydrological systems respond to and cope with perturbations and how these connect to resilience remain unanswered. In this opinion paper, we propose a novel conceptual framework for understanding and assessing resilience in coupled socio-hydrological contexts, and encourage debate on the inter-connections between socio-hydrology and resilience. Taking a systems perspective, we argue that resilience is a set of systematic properties with three dimensions: absorptive, adaptive, and transformative, and contend that socio-hydrological systems can be viewed as various forms of human-water couplings, reflecting different aspects of these interactions. We propose a framework consisting of two parts. The first part addresses the identity of socio-hydrological resilience, answering questions such as "resilience of what in relation to what". We identify three existing framings of resilience for different types of human-water systems and subsystems, which have been used in different fields: (1) the water subsystem, highlighting hydrological resilience to anthropogenic hazards; (2) the human subsystem, foregrounding social resilience to hydrological hazards; and (3) the coupled human-water system, exhibiting socio-hydrological resilience. We argue that these three system types and resiliences afford new insights into the clarification and evaluation of different water management challenges. The first two types address hydrological and social states, while the third type emphasises the feedbacks and interactions between human and water components within complex systems subject to internal or external disturbances. In the second part, we focus on resilience management and develop the notion of the "resilience canvas", a novel heuristic device to identify possible pathways and to facilitate the design of bespoke strategies for enhancing resilience in the socio-hydrological context. The resilience canvas is constructed by combining absorptive and adaptive capacities as two axes. At the corners of the resulting twodimensional space are four quadrants which we conceptualise as representing resilient, vulnerable, susceptible, and resistant system states. To address projected change-induced uncertainties, we recommend that efforts now be focused on shifting socio-hydrological systems from resistant towards resilient status. In sum, the novel framework proposed here clarifies the ambiguity inherent in socio-hydrological resilience, and provides a viable basis for further theoretical and practical development.

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“…As such, this approach has been widely applied in preclinical models and clinical trials. oHSVs armed with immunomodulators continue to be popular among oHSV laboratories, and continue to be studied in ongoing clinical and preclinical investigations of oHSV therapy (94,96,(98)(99)(100)(101)(102)(103).…”

Section: Arming Vectors: Insertion Of Genes Encoding For Anticancer Pmentioning

confidence: 99%

Oncolytic herpes simplex virus 1 (HSV-1) vectors: Increasing treatment efficacy and range through strategic virus design

Carson¹,

Haddad²,

Bressman³

et al. 2010

Drugs Fut

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SUMMARYViruses have long been considered potential anticancer treatments. Wild-type viruses have been tested as anticancer agents in clinical trials since the 1960s. The possibility of viral oncolysis as an alternate cancer therapy was transformed by the emergence of modern genetic engineering. The herpes simplex virus (HSV) family offers particular advantages for use as a viral oncolytic. The engineered vectors that make up oncolytic HSVs (oHSVs) have demonstrated remarkable safety in clinical trials, with some evidence of efficacy. The past decade has seen a focus on increasing the efficacy of oncolytic vectors by adding exogenous transgenes to enhance tumor destruction. The current paper describes the various strategies for engineering HSV for increased cancer tissue specificity and efficacy. Presented are the rationale, preclinical data and clinical data where available. This is meant to illustrate a basic framework for the development of a novel therapy meant to exploit the viral life cycle for the killing of cancer.

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Use of an oncolytic virus secreting GM-CSF as combined oncolytic and immunotherapy for treatment of colorectal and hepatic adenocarcinomas

Cited by 71 publications

References 33 publications

Oncolytic plasmid: A novel strategy for tumor immuno-gene therapy

Oncolytic plasmid: A novel strategy for tumor immuno-gene therapy

HESS Opinions: A conceptual framework for assessing socio-hydrological resilience under change

Oncolytic herpes simplex virus 1 (HSV-1) vectors: Increasing treatment efficacy and range through strategic virus design

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