Abscopal effect when combining oncolytic adenovirus and checkpoint inhibitor in a humanized NOG mouse model of melanoma

Kuryk, Łukasz; Møller, Anne‐Sophie W.; Jäderberg, Magnus

doi:10.1002/jmv.25501

Cited by 43 publications

(40 citation statements)

References 29 publications

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“…Hence, in the current study, we set to investigate whether the systemic administration of cancer derived EVs is able to deliver theranostics to early stage mammary cancers generated in a genetic mouse model of breast cancer (MMTV-NeuT mice) [16]. For these experiments, we encapsulated into EVs a diagnostic fluorescent dye [17] and an oncolytic virus [18][19][20][21] as tracking agents for the characterization of the whole-body biodistribution of the formulations. Herein, we show that cancer-derived EVs are able to target the mammary glands in MMTV-NeuT mice as soon as they start developing a neoplastic tissue, thus suggesting the possibility to deliver theranostic cargos of EVs also to early stage neoplasia.…”

Section: Ivyspringmentioning

confidence: 99%

Cancer-derived EVs show tropism for tissues at early stage of neoplastic transformation

et al. 2021

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From the past decade, extracellular vesicles (EVs) have attracted considerable attention as tools for the selective delivery of anti-neoplastic drugs to cancer tissues. Compared to other nanoparticles, EVs display interesting unique features including immune compatibility, low toxicity and the ability to encapsulate a large variety of small-and macro-molecules. However, in virtually all studies, investigations on EVs have been focused on fully transformed cancers: the possibility to apply EV technology also to early-stage tumors has never been explored. Methods: Herein, we studied the ability of cancer-derived EVs to recognize and deliver their cargo also to incipient cancers. To this purpose, EV biodistribution was studied in MMTV-NeuT genetically modified mice during early mammary transformation, in fully developed breast tumors and in the normal gland of wild type syngeneic mice. EVs were loaded with indocyanine green (ICG), a near-infrared (NIR) dye together with oncolytic viruses and i.v. injected in mice. The nanoparticle biodistribution was assayed by in vivo and ex vivo optical imaging (detecting the ICG) and semiquantitative real-time PCR (measuring the adenoviral genome) in different tissues. Results: Our results demonstrate the ability of cancer-derived EVs to recognize early-stage neoplastic tissues opening the possibility to selectively deliver theranostics also for tumor prevention. Conclusions: Taken together our study demonstrates the ability of EVs to recognize and deliver diagnostic and therapeutic agents not only to fully transformed tissues but also to early stage tumors. These findings pave the way for the synthesis of "universal" EVs-based formulation for targeted cancer therapy.

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Section: Ivyspringmentioning

confidence: 99%

Cancer-derived EVs show tropism for tissues at early stage of neoplastic transformation

et al. 2021

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“…The two most important immune checkpoints that have been studied in immunotherapy are the cytotoxic-T lymphocytes antigen 4 (CTLA-4) and the programmed cell death protein 1 (PD-1) [ 44 , 45 ]. CTLA-4 is a receptor and a member of the immunoglobulin superfamily CD28:B7 [ 46 ].…”

Section: Cancer Immunotherapymentioning

confidence: 99%

“…The combination of anti-PD1 with the virus further reduced tumor volume, while pembrolizumab alone did not show therapeutic benefit by itself [ 45 ]. Systemic abscopal was also observed when combining oncolytic adenovirus and checkpoint inhibitor in a humanized NOG mouse model of melanoma [ 44 ]. These data support the scientific rationale for the ongoing clinical study of combination therapy of ONCOS-102 and pembrolizumab for the treatment of melanoma (NCT03003676).…”

Section: Combinatorial Approaches With Ovs In Melanoma Treatmentsmentioning

confidence: 99%

From Conventional Therapies to Immunotherapy: Melanoma Treatment in Review

Kuryk

Bertinato

Staniszewska

et al. 2020

Cancers

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In this review, we discuss the use of oncolytic viruses and checkpoint inhibitors in cancer immunotherapy in melanoma, with a particular focus on combinatory therapies. Oncolytic viruses are promising and novel anti-cancer agents, currently under investigation in many clinical trials both as monotherapy and in combination with other therapeutics. They have shown the ability to exhibit synergistic anticancer activity with checkpoint inhibitors, chemotherapy, radiotherapy. A coupling between oncolytic viruses and checkpoint inhibitors is a well-accepted strategy for future cancer therapies. However, eradicating advanced cancers and tailoring the immune response for complete tumor clearance is an ongoing problem. Despite current advances in cancer research, monotherapy has shown limited efficacy against solid tumors. Therefore, current improvements in virus targeting, genetic modification, enhanced immunogenicity, improved oncolytic properties and combination strategies have a potential to widen the applications of immuno-oncology (IO) in cancer treatment. Here, we summarize the strategy of combinatory therapy with an oncolytic vector to combat melanoma and highlight the need to optimize current practices and improve clinical outcomes.

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“…Therefore, its use for treatment of metastases, which kills the majority of cancer patients, is limited. Metastasis treatment would require blood system disseminated therapy to individually target each lesion through intravenous (IV) delivery, or utilizing the abscopal effect from treatment of one or more lesions, which could lead to a systemic anti-tumour immune response extending to the milieu of micro metastatic deposits in the body [26][27][28]. Therefore, significant research is ongoing into other viral vectors that may be better suited to IV delivery, including adenovirus (Ads) [29], reovirus [30] and vaccinia virus [31].…”

Section: Adenovirus As An Oncolytic Virotherapymentioning

confidence: 99%

Hitting the Target but Missing the Point: Recent Progress Towards Adenovirus-Based Precision Virotherapies

Cunliffe

Bates

Parker

2020

Preprint

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More people are surviving longer with cancer. Whilst this can be partially attributed to advances in early detection of cancers, there is little doubt that the improvement in survival statistics is also due to the expansion in the spectrum of treatments available for efficacious treatment. Transformative amongst those are immunotherapies, which have proven effective agents for treating immunogenic forms of cancer, though immunologically “cold” tumour types remain refractive. Oncolytic viruses, such as those based on adenovirus have great potential as anti-cancer agents and have seen a resurgence of interest in recent years. Amongst their many advantages is their ability to induce immunogenic cell death (ICD) of infected tumour cells, thus providing the alluring potential to synergize with immunotherapies by turning immunologically “cold” tumours “hot”. Additionally, enhanced immune mediated cell killing can be promoted through the local overexpression of immunological transgenes, encoded from within the engineered viral genome. To achieve this full potential requires the development of refined, tumour selective “precision virotherapies” that are extensively engineered to prevent off-target up take via native routes of infection, and targeted to infect and replicate uniquely within malignantly transformed cells. Here, we review the latest advances towards this holy grail within the adenoviral field.

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Abscopal effect when combining oncolytic adenovirus and checkpoint inhibitor in a humanized NOG mouse model of melanoma

Cited by 43 publications

References 29 publications

Cancer-derived EVs show tropism for tissues at early stage of neoplastic transformation

Cancer-derived EVs show tropism for tissues at early stage of neoplastic transformation

From Conventional Therapies to Immunotherapy: Melanoma Treatment in Review

Hitting the Target but Missing the Point: Recent Progress Towards Adenovirus-Based Precision Virotherapies

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