Oncolytic Viruses Expressing Cytokine IL-36γ for Cancer Therapy

Novel oncolytic vaccinia viruses were constructed to express the secreted form of IL-36γ. The virus infects cancer cells, induces oncolysis, and secretes the cytokine from the infected cancer cells. The addition of IL-36γ enhances the antitumor activities of the oncolytic viruses by promoting an adaptive T cell-mediated immune response and stimulating the immunogenic tumor microenvironment. In models of colon cancer, pancreatic cancer, and melanoma, direct injection of the armed virus led to superior antitumor effects.

Description

Although its therapeutic potential is promising, oncolytic virotherapy, in which tumor-targeted viruses are used to destroy cancer cells, has so far shown limited efficacy in cancer patients and preclinical studies are largely focused on improving therapeutic potency. Dr. Binfeng Lu’s group at the University of Pittsburgh has previously shown that expression of cytokine IL-36γ leads to activated antitumor immunity and inhibited tumor growth. Combining the two approaches has the potential to increase the therapeutic potency of both treatments.

Applications

• Treating cancer

Advantages

• Tumor-targeting oncolytic viruses prevent the risk of drug toxicity by avoiding systemic administration of IL-36γ.
• Addition of cytokine IL-36γ increases the potency and therapeutic potential of oncolytic virotherapy.

Invention Readiness

In vitro data

IP Status

https://patents.google.com/patent/US20220211814A1

Related Publication(s)

Ye, J.; Chen, L.; Waltermire, J.; Zhao, J.; Ren, J.; Guo, Z.; Bartlett, D.L.; Liu, Z. Intratumoral Delivery of Interleukin 9 via Oncolytic Vaccinia Virus Elicits Potent Antitumor Effects in Tumor Models. Cancers 2024, 16, 1021. https://doi.org/10.3390/cancers16051021

Zhu, Z., McGray, A.J.R., Jiang, W. et al. Improving cancer immunotherapy by rationally combining oncolytic virus with modulators targeting key signaling pathways. Mol Cancer 21, 196 (2022). https://doi.org/10.1186/s12943-022-01664-z

Yang, M., Giehl, E., Feng, C., Feist, M., Chen, H., Dai, E., Liu, Z., Ma, C., Ravindranathan, R., Bartlett, D. L., Lu, B., & Guo, Z. S. (2021). IL-36γ-armed oncolytic virus exerts superior efficacy through induction of potent adaptive antitumor immunity. Cancer Immunology, Immunotherapy, 70(9), 2467–2481. https://doi.org/10.1007/s00262-021-02860-4