While cure rates for several cancers have significantly improved over the last decades, the outcome for patients with advanced solid tumors remains grimly unchanged, underscoring the need for new therapies. Oncolytic (cancer destroying) vaccinia virus (VV) is an appealing addition to the current cancer therapies due to its preference for infecting and killing tumor cells and a potential for activating the immune system component called T-cells that can travel to distant sites and kill any tumor cells they find, even those not infected by the virus.

At present, a desirable systemic intravenous administration of the virus is not feasible due to the strong immune response against it. In addition...

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While cure rates for several cancers have significantly improved over the last decades, the outcome for patients with advanced solid tumors remains grimly unchanged, underscoring the need for new therapies. Oncolytic (cancer destroying) vaccinia virus (VV) is an appealing addition to the current cancer therapies due to its preference for infecting and killing tumor cells and a potential for activating the immune system component called T-cells that can travel to distant sites and kill any tumor cells they find, even those not infected by the virus.

At present, a desirable systemic intravenous administration of the virus is not feasible due to the strong immune response against it. In addition, virus spread within the tumor as well as the activation of T-cells is suboptimal. In our proposal we will engineer a VV by (i) making the necessary modifications within the VV proteins to mask it against immune system, making it suitable for systemic delivery, and (ii) secreting a new molecule called a T-cell engager that couples T cells to the tumor cells increasing the effectiveness of the T cells and their activation.

Our therapy will target solid tumors in humans, including melanoma, breast cancer, colorectal cancer, pancreatic adenocarcinoma, and ovarian cancer and is expected to have a major impact on the treatment of advanced, metastatic tumors, which are often incurable with current treatment strategies.

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