Harnessing MEM-288: A Dual-Transgene Oncolytic Adenovirus for Targeted Cancer Therapy

3 June 2024
MEM-288 is an innovative oncolytic adenovirus engineered for the treatment of solid and liquid tumors, either as a monotherapy or in combination with immune checkpoint inhibitors (ICIs). It features multiple enhancements for tumor-selective replication, including delta-24 (Δ24) E1, E1b 55kb, and E3 deletions. The virus is equipped with two immune-stimulating transgenes: MEM40, a stable cell surface-expressed chimeric CD40 ligand (CD40L) that activates dendritic cells (DCs), and IFNβ, which aids in the maturation and activation of DCs and T cells.

Designed to surpass the limitations of conventional oncolytic viruses (OVs), MEM-288 has demonstrated significantly heightened tumor selectivity, oncolytic potency, and the capacity to boost DC and T cell functionality. It has shown approximately 100-fold greater replication and oncolytic action in various human tumor cell lines compared to control adenoviruses. MEM-288 also displayed a substantial preference for tumor cells over normal cells, including a 1,000-fold higher viral replication rate in tumor cells.

In vivo studies in immunocompetent mouse models have confirmed MEM-288's promising anti-metastatic activity and its ability to control both injected and non-injected tumors in melanoma models. The virus showed superior inhibition of tumor growth compared to the combination of anti-CTLA4 and PD-1 antibodies. Furthermore, the combination of MEM-288 with these ICIs led to enhanced anti-tumor effects, complete tumor regressions, and 100% mouse survival at day 30, a significant improvement over individual treatments.

In the B16-OVA melanoma model, MEM-288 induced superior T cell clonal expansion compared to a control OV, highlighting the critical role of IFNβ in T cell activation when combined with MEM40. These findings indicate that MEM-288 is a potent, tumor-selective oncolytic virus with unique features that make it a strong candidate for combination therapy with ICIs, even in refractory settings. The virus is under consideration for clinical evaluation for lung cancer and other tumor types.

How to Use Synapse Database to Search and Analyze Translational Medicine Data?

The transational medicine section of the Synapse database supports searches based on fields such as drug, target, and indication, covering the T0-T3 stages of translation. Additionally, it offers a historical conference search function as well as filtering options, view modes, translation services, and highlights summaries, providing you with a unique search experience.

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Taking obesity as an example, select "obesity" under the indication category and click search to enter the Translational Medicine results list page. By clicking on the title, you can directly navigate to the original page.

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By clicking the analysis button, you can observe that GLP-1R treatment for obesity has gained significant attention over the past three years, with preclinical research still ongoing in 2023. Additionally, there are emerging potential targets, such as GDF15, among others.

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Click on the image below to go directly to the Translational Medicine search interface.

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