Combination therapy with oncolytic viruses and immune checkpoint inhibitors

Chiu, Matthew; Armstrong, Edward John Lloyd; Jennings, Vicki; Foo, Shane; Crespo-Rodriguez, Eva; Bozhanova, Galabina; Patin, Emmanuel C.; McLaughlin, Martin; Mansfield, David; Baker, Gabriella; Grove, Lorna; Pedersen, Malin; Kyula, Joan; Roulstone, Victoria; Wilkins, Anna; McDonald, Fiona; Harrington, Kevin; Melcher, Alan

doi:10.1080/14712598.2020.1729351

Cited by 40 publications

(30 citation statements)

References 144 publications

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“…However, unfortunately, from 40%–60% of melanoma patients do not gain any significant therapeutic benefit and a profound proportion of responders observe tumor relapse within 2 years [ 9 , 10 , 11 ]. The response rates to ICI monotherapy are low, in part due to the presence of a “cold” immune tumor microenvironment (TME) [ 12 ]. Consequently, novel and more efficient therapeutics strategies and synergistic combination therapies are in high demand [ 9 , 12 ].…”

Section: Introductionmentioning

confidence: 99%

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Combination Therapy of Novel Oncolytic Adenovirus with Anti-PD1 Resulted in Enhanced Anti-Cancer Effect in Syngeneic Immunocompetent Melanoma Mouse Model

et al. 2021

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Malignant melanoma, an aggressive form of skin cancer, has a low five-year survival rate in patients with advanced disease. Immunotherapy represents a promising approach to improve survival rates among patients at advanced stage. Herein, the aim of the study was to design and produce, by using engineering tools, a novel oncolytic adenovirus AdV-D24- inducible co-stimulator ligand (ICOSL)-CD40L expressing potent co-stimulatory molecules enhancing clinical efficacy through the modulation of anti-cancer immune responses. Firstly, we demonstrated the vector’s identity and genetic stability by restriction enzyme assay and sequencing, then, by performing in vitro and in vivo pre-clinical studies we explored the anti-cancer efficacy of the virus alone or in combination with anti PD-1 inhibitor in human melanoma cell lines, i.e., MUG Mel-1 and MUG Mel-2, and in immunocompetent C57BL/6 melanoma B16V mouse model. We showed that both monotherapy and combination approaches exhibit enhanced anti-cancer ability and immunogenic cell death in in vitro settings. Furthermore, AdV-D24-ICOSL-CD40L combined with anti PD-1 revealed a fall in tumor volume and 100% survival in in vivo context, thus suggesting enhanced efficacy and survival via complementary anti-cancer properties of those agents in melanoma therapy. Collectively, the novel oncolytic vector AdV-D24-ICOSL-CD40L alone or in combination with anticancer drugs, such as check point inhibitors, may open novel therapeutic perspectives for the treatment of melanoma.

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Section: Introductionmentioning

confidence: 99%

“…The response rates to ICI monotherapy are low, in part due to the presence of a “cold” immune tumor microenvironment (TME) [ 12 ]. Consequently, novel and more efficient therapeutics strategies and synergistic combination therapies are in high demand [ 9 , 12 ].…”

Section: Introductionmentioning

confidence: 99%

Combination Therapy of Novel Oncolytic Adenovirus with Anti-PD1 Resulted in Enhanced Anti-Cancer Effect in Syngeneic Immunocompetent Melanoma Mouse Model

et al. 2021

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“…While our understanding of how to capture the full potential of oncolytic virotherapy continues to evolve, it appears clear that release of tumor associated antigens and activation of the immune system is crucial for these anti-oncolytic agents. Consequently, combinations of oncolytic viruses with immune checkpoint inhibitors are dominating the current clinical trial landscape [ 295 , 296 ]. However, combinations with select small molecule compounds can address some of the limitations of the oncolytic core features and improve oncolysis, intra-tumoral spread, immunogenicity of tumor cell killing, as well as improving antigen processing and the regulation of immune cell populations.…”

Section: Discussionmentioning

confidence: 99%

Combining Oncolytic Viruses and Small Molecule Therapeutics: Mutual Benefits

Spiesschaert

Angerer

Park

et al. 2021

Cancers

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The focus of treating cancer with oncolytic viruses (OVs) has increasingly shifted towards achieving efficacy through the induction and augmentation of an antitumor immune response. However, innate antiviral responses can limit the activity of many OVs within the tumor and several immunosuppressive factors can hamper any subsequent antitumor immune responses. In recent decades, numerous small molecule compounds that either inhibit the immunosuppressive features of tumor cells or antagonize antiviral immunity have been developed and tested for. Here we comprehensively review small molecule compounds that can achieve therapeutic synergy with OVs. We also elaborate on the mechanisms by which these treatments elicit anti-tumor effects as monotherapies and how these complement OV treatment.

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“…To date, approximately one third of all clinical trials concerning OVs have investigated a combinatorial approach with at least one ICI [ 91 ]. Therefore, it is expected that oncolytic viruses have the capability to promote a ‘hotter’ immune microenvironment which can improve the efficacy of ICI [ 103 , 104 ]. Oncolytic viruses can be thought of as matches—they can light up a fire inside the tumor and this fire will make the TME “hot” enough for ICIs to strike a blow.…”

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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Combination therapy with oncolytic viruses and immune checkpoint inhibitors

Cited by 40 publications

References 144 publications

Combination Therapy of Novel Oncolytic Adenovirus with Anti-PD1 Resulted in Enhanced Anti-Cancer Effect in Syngeneic Immunocompetent Melanoma Mouse Model

Combination Therapy of Novel Oncolytic Adenovirus with Anti-PD1 Resulted in Enhanced Anti-Cancer Effect in Syngeneic Immunocompetent Melanoma Mouse Model

Combining Oncolytic Viruses and Small Molecule Therapeutics: Mutual Benefits

From Conventional Therapies to Immunotherapy: Melanoma Treatment in Review

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