Oncolytic Adenoviruses in Cancer Treatment

Alemany, Ramón

doi:10.3390/biomedicines2010036

Cited by 36 publications

(27 citation statements)

References 60 publications

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“…One potential obstacle with these approaches is that oncolytic viruses can drive an anti‐viral immune response which may divert the immune system from tumor‐specific antigens; a process called “immunodominance” (Alemany, 2014). Immunodominance occurs because the large numbers of viral peptides introduced into the patient overwhelm the APC system, thereby diverting APCs from TAAs.…”

Section: Introductionmentioning

confidence: 99%

In situ vaccination: Cancer immunotherapy both personalized and off‐the‐shelf

2015

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As cancer immunotherapy continues to benefit from novel approaches which cut immune 'brake pedals' (e.g. anti-PD1 and anti-CTLA4 antibodies) and push immune cell gas pedals (e.g. IL2, and IFNα) there will be increasing need to develop immune 'steering wheels' such as vaccines to guide the immune system specifically toward tumor associated antigens. Two primary hurdles in cancer vaccines have been: identification of universal antigens to be used in 'off-the-shelf' vaccines for common cancers, and 2) logistical hurdles of ex vivo production of individualized whole tumor cell vaccines. Here we summarize approaches using 'in situ vaccination' in which intratumoral administration of off-the-shelf immunomodulators have been developed to specifically induce (or amplify) T cell responses to each patient's individual tumor. Clinical studies have confirmed the induction of systemic immune and clinical responses to such approaches and preclinical models have suggested ways to further potentiate the translation of in situ vaccine trials for our patients.

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Section: Introductionmentioning

confidence: 99%

In situ vaccination: Cancer immunotherapy both personalized and off‐the‐shelf

2015

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“…Ads are non-enveloped DNA viruses with an icosahedral capsid encompassing a linear duplex genome of ~36 kb. Ads have been found in the majority of vertebrates [ 3 ]. Human Ads are ubiquitous in the environment and have been classified into 57 serotypes (Ad1-Ad57) based on cross-susceptibility to neutralizing antibodies and seven subgroups (A–G).…”

Section: Oncolytic Adenoviral Platform Developmentmentioning

confidence: 99%

“…Although the initial research was conducted with Ad5, natural tropism and seroprevalence are becoming critical factors for vector success. A number of Ad subgroups can provide natural GI tropism such as the subgroup A (Ad12), and subgroup F (Ad40, Ad 41) [ 3 ]. The Ad12 E1B protein had similarities with A-gliadin and was studied as a factor in the development of gluten intolerance [ 7 ].…”

Section: Oncolytic Adenoviral Platform Developmentmentioning

confidence: 99%

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Oncolytic Adenoviruses in Gastrointestinal Cancers

2018

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Gastrointestinal malignancies are challenging cancers with considerable economic and societal impacts on health care systems worldwide. While advances in surgical approaches have provided benefits to a proportion of patients, only modest improvements have been attained in the treatment of patients with advanced disease, resulting in limited improvement in survival rates in these patients. Oncolytic adenoviruses are being developed to address gastrointestinal malignancies. Each platform has evolved to maximize tumor-cell killing potency while minimizing toxicities. Tumor-specific bioengineered adenoviruses using chimeric promoters, prodrug convertase enzymes, lethal genes, tumor suppressor genes, and pseudo-typed capsids can provide the innovations for eventual success of oncolytic virotherapy. This article will review the developments in adenoviral platforms in the context of specific gastrointestinal cancers. From the bench to the implementation of clinical trials, this review aims to highlight advances in the field from its early days to the current state of affairs as it pertains to the application of adenoviral oncolytic therapy to gastrointestinal cancers.

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“…Oncolysis of tumor cells after OAd infection releases pattern and damage-associated molecular patterns (PAMPs and DAMPs) and tumor-associated antigens (TAAs) that stimulate the immune response and enhance anti-tumor activity through epitope spreading or antigen cascade with limited clinical pathologies [6]. However, due to the heterogenous and complex nature of most solid tumors, OAd-mediated lysis is not sufficient to fully eliminate disease.…”

Section: Introductionmentioning

confidence: 99%

Modeling the Efficacy of Oncolytic Adenoviruses In Vitro and In Vivo: Current and Future Perspectives

McKenna

Shaw

Suzuki

2020

Cancers

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Oncolytic adenoviruses (OAd) selectively target and lyse tumor cells and enhance antitumor immune responses. OAds have been used as promising cancer gene therapies for many years and there are a multitude of encouraging pre-clinical studies. However, translating OAd therapies to the clinic has had limited success, in part due to the lack of realistic pre-clinical models to rigorously test the efficacy of OAds. Solid tumors have a heterogenous and hostile microenvironment that provides many barriers to OAd treatment, including structural and immunosuppressive components that cannot be modeled in two-dimensional tissue culture. To replicate these characteristics and bridge the gap between pre-clinical and clinical success, studies must test OAd therapy in three-dimensional culture and animal models. This review focuses on current methods to test OAd efficacy in vitro and in vivo and the development of new model systems to test both oncolysis and immune stimulatory components of oncolytic adenovirotherapy. Author Contributions: Conceptualization, M.S.; Writing-Original Draft, M.K.M.; Writing-Review and Editing, M.K.M., A.R.-S. and M.S.; Supervision, M.S.; Funding Acquisition, M.S. All authors have read and agreed to the published version of the manuscript.

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Oncolytic Adenoviruses in Cancer Treatment

Cited by 36 publications

References 60 publications

In situ vaccination: Cancer immunotherapy both personalized and off‐the‐shelf

In situ vaccination: Cancer immunotherapy both personalized and off‐the‐shelf

Oncolytic Adenoviruses in Gastrointestinal Cancers

Modeling the Efficacy of Oncolytic Adenoviruses In Vitro and In Vivo: Current and Future Perspectives

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