Preexisting immunity: Barrier or bridge to effective oncolytic virus therapy?

Groeneveldt, Christianne; Ende, Jasper van den; Montfoort, Nadine van

doi:10.1016/j.cytogfr.2023.01.002

Cited by 20 publications

(15 citation statements)

References 130 publications

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“…Currently, the widely accepted viewpoint maintains that pre-existing immunity attenuates the efficacy of OVs upon systematic administration, primarily due to the acceleration of viral clearance. 12 Although OVs are unaffected by pre-existing antibodies after intratumoral injection, from a clinical perspective, administration of OVs systematically is more favorable as it not only alleviates patient discomfort but also can be used for tumors that are inaccessible for intratumoral injection. 12 Building on previous discussions, Exos secreted by cancer cells subsequent to miR-CVB3 infection encapsulate miR-CVB3 and are enriched with robust immunostimulatory properties that distinguish them from the typical Exos released by cancer cells (Figure 1F).…”

Section: Exos Released By Cancer Cells After Mir-cvb3 Infection Can S...mentioning

confidence: 99%

“…12 Although OVs are unaffected by pre-existing antibodies after intratumoral injection, from a clinical perspective, administration of OVs systematically is more favorable as it not only alleviates patient discomfort but also can be used for tumors that are inaccessible for intratumoral injection. 12 Building on previous discussions, Exos secreted by cancer cells subsequent to miR-CVB3 infection encapsulate miR-CVB3 and are enriched with robust immunostimulatory properties that distinguish them from the typical Exos released by cancer cells (Figure 1F). Moreover, these Exos, referred to as ExomiR-CVB3, exhibit increased levels of CD47 that acts as a "do not eat me" signal.…”

Section: Exos Released By Cancer Cells After Mir-cvb3 Infection Can S...mentioning

confidence: 99%

“…To evaluate the pH-dependent release kinetics of Dox, ExomiR-CVB3/DoxApt was immersed in both phosphate buffered saline and sodium acetate buffer (with pH values of 7.4 and 5.5, respectively). The release of Dox into the buffer from ExomiR-CVB3/DoxApt was measured at different time intervals (1,3,6,12,18,24, and 36 h) using a SpectraMax iD3 microplate reader. Calculations for the cumulative release percentage (AR %) of Dox were determined using the equation AR % = D 1 /D 0 × 100, (D 1 = concentration of released Dox and D 0 = the initial concentration of Dox loaded onto ExomiR-CVB3/DoxApt).…”

Section: % Ee (Initial Amount Of Dox Amount Of Dox In Supernatant)mentioning

confidence: 99%

“…A rational approach to address this is systemic delivery. However, the effectiveness of this delivery method is hampered by the presence of neutralizing antibodies and rapid clearance of OVs after intravenous or intraperitoneal injection. , To tackle these challenges, scientists have endeavored to create innovative carriers for OVs . These include cellular carriers like mesenchymal stromal cells and osteosarcoma cells, alongside nanomaterials such as nanogold, graphene oxides, and liposomes. , …”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Synergistic Viro-chemoimmunotherapy in Breast Cancer Enabled by Bioengineered Immunostimulatory Exosomes and Dual-Targeted Coxsackievirus B3

Bahreyni,

Mohamud,

Ashraf Nouhegar

et al. 2024

ACS Nano

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Breast cancer's immunosuppressive environment hinders effective immunotherapy, but oncolytic viruses hold promise for addressing this challenge by targeting tumor cells and altering the microenvironment. Yet, neutralizing antibodies and immune clearance impede their clinical utility. This study explored microRNA-modified coxsackievirus B3 (miR-CVB3), an innovative oncolytic virus, and its potential in breast cancer treatment. It investigated miR-CVB3's impact on immune-related proteins and utilized exosomes as both protective shields and delivery carriers. Results demonstrated miR-CVB3's capacity to reshape immune-related protein profiles toward a more immunostimulatory state and enhance exosome-mediated immune cell activation. Notably, cancer cell-released exosomes encapsulating miR-CVB3 (ExomiR-CVB3) maintained its antitumor cytotoxicity and bolstered its immunostimulatory effects. Moreover, ExomiR-CVB3 shielded miR-CVB3 from neutralizing antibodies and rapid immune clearance when it was systemically administered. Building on these findings, ExomiR-CVB3 was engineered with the AS1411 aptamer and doxorubicin (ExomiR-CVB3/DoxApt), enhancing therapeutic efficacy. This notable approach, combining genomic modification, aptamer surface decoration, and doxorubicin addition, demonstrated safe delivery of CVB3 to cancer cells. Comprehensive in vitro and in vivo analyses revealed selective breast cancer cell targeting, cell death induction, and significant immune cell infiltration within the tumor microenvironment while sparing healthy organs. In summary, this study highlights ExomiR-CVB3/DoxApt as a pioneering breast cancer treatment strategy adaptable for diverse cancer types, offering a potent and versatile approach to reshaping cancer immunotherapy.

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Section: Exos Released By Cancer Cells After Mir-cvb3 Infection Can S...mentioning

confidence: 99%

Section: Exos Released By Cancer Cells After Mir-cvb3 Infection Can S...mentioning

confidence: 99%

Section: % Ee (Initial Amount Of Dox Amount Of Dox In Supernatant)mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Synergistic Viro-chemoimmunotherapy in Breast Cancer Enabled by Bioengineered Immunostimulatory Exosomes and Dual-Targeted Coxsackievirus B3

Bahreyni,

Mohamud,

Ashraf Nouhegar

et al. 2024

ACS Nano

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“…In the clinic, Reo has demonstrated limited potential when applied as monotherapy ( 4–6 ). Although various aspects might contribute to this limited efficacy, one potential barrier to the clinical success of Reo is preexisting immunity against the virus ( 7 ). The majority of individuals acquire preexisting immunity against reovirus after non-symptomatic exposure, and this is indicated by the detection of neutralizing antibodies (NAb) in patient sera before treatment with Reo ( 5, 8–12 ).…”

Section: Introductionmentioning

confidence: 99%

Neutralizing Antibodies Impair the Oncolytic Efficacy of Reovirus but Permit Effective Combination with T cell–Based Immunotherapies

Groeneveldt,

Kinderman,

Griffioen

et al. 2024

Cancer Immunology Research

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Reovirus type 3 Dearing (Reo), manufactured for clinical application as Pelareorep, is an attractive anticancer agent under evaluation in multiple phase 2 clinical trials for the treatment of solid tumors. It elicits its anticancer efficacy by inducing both oncolysis and intratumoral T-cell influx. Since most people have been preexposed to Reo, neutralizing antibodies (NAbs) are prevalent in cancer patients and might present a barrier to effective Reo therapy. Here, we tested serum of cancer patients and healthy controls (n=100) and confirmed that Reo NAbs are present in >80% of individuals. To investigate the effect of NAbs on both the oncolytic and the immunostimulatory efficacy of Reo, we established an experimental mouse model with Reo preexposure. The presence of preexposure-induced NAbs reduced Reo tumor infection and prevented Reo-mediated control of tumor growth after intratumoral Reo administration. In B cell–deficient mice, the lack of NAbs provided enhanced tumor growth control after Reo monotherapy, indicating NAbs limit the oncolytic capacity of Reo. In immunocompetent mice, intratumoral T-cell influx was not affected by the presence of preexposure-induced NAbs and consequently, combinatorial immunotherapy strategies comprising Reo and T-cell engagers or checkpoint inhibitors remained effective in these settings, also after a clinically-applied regimen of multiple intravenous Pelareorep administrations. Altogether, our data indicate that NAbs hamper the oncolytic efficacy of Reo, but not its immunotherapeutic capacity. Given the high prevalence of seropositivity for Reo in cancer patients, our data strongly advocate for the application of Reo as part of T cell–based immunotherapeutic strategies.

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