Biomedicine Seminar

Oncolytic virotherapy represents a distinctive immunotherapeutic strategy to eradicate malignancies, where viral agents are engineered to selectively target cancer cells. By leveraging their oncolytic properties and the subsequent release of tumor antigens, these viruses convert the tumor microenvironment into an immunologically active state, thus enhancing the immune recognition of the tumor. Among oncolytic agents, Vesicular Stomatitis Virus D51 (VSVD51) stands out for its robust oncolytic capabilities and the lack of pre-existing immunity in patients. Specifically, VSVD51 originates as an agricultural pathogen, which is modified to be highly sensitive to interferon (IFN) action enhancing its safety for clinical applications. Despite these promising attributes, VSVD51 has encountered obstacles in clinical translation, primarily stemming from the heterogeneous nature of cancer diseases. Notably, some tumor cells retain intact IFN signaling, rendering them resistant to VSVD51 infection. To address this challenge, our research implements innovative strategies to augment the efficacy of oncolytic VSVD51 therapy through the incorporation of electrophilic compounds.

Previously, we identified 4-Octyl-Itaconate, an electrophilic metabolite-derived drug capable of dampening antiviral IFN signaling by directly targeting MAVS and IKKb. Consequently, this compound significantly bolstered VSVD51-mediated oncolysis both in in vitro and in vivo settings, displaying promising anticancer strategy. In addition, the implementation of pathologically relevant cancer models such as patient derived 3D tumoroids made the study highly translational. Furthermore, through a comprehensive library screening of electrophilic small fragments, we pinpointed a specific fragment, designated as "X," which sensitized oncolytic viruses by directly engaging the sterol carrier protein SCPx and suppressing IFN antiviral response.

Overall, our findings suggest that combining electrophilic compounds/fragments with direct protein targeting capabilities alongside oncolytic virus agents holds tremendous potential for enhancing anticancer therapeutic outcomes. By harnessing the synergistic effects of these modalities, we aim to overcome existing limitations and pave the way for more precise and effective cancer treatments.

Venue:
The seminar will be held at 12:00 pm in 1231-424, Lille Anatomisk Auditorium.

The talk is 45 minutes followed by 15 minutes of discussion, for a total of 1 hr.

Zoom link, for those of you who cannot attend in person: 
https://aarhusuniversity.zoom.us/j/66672312099
Meeting ID: 666 7231 2099

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Biomedicine seminar organizing committee.
Mikkel Vendelbo
Line Reinert
Søren Egedal Degn 
Martin Kristian Thomsen