US Food and Drug Administration (FDA) has recently approved a type I herpes simplex virus (HSV-1) based oncolytic virus, T-VEC (Imlygic), for treatment of melanoma. This is the first FDA approval for virotherapy, a new type of cancer treatment that is based a pragmatic therapeutic principle - purposefully modifying a virus so that it can selectively kill malignant cells. My laboratory has employed a novel mechanism to create a HSV-2-based oncolytic virus, the first of this kind (all other oncolytic HSVs, including, T-VEC are constructed from HSV-1). Designated FusOn-H2, it showed potent activity against many tumor types, including breast cancer, pancreatic cancer, ovarian cancer and prostate...

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US Food and Drug Administration (FDA) has recently approved a type I herpes simplex virus (HSV-1) based oncolytic virus, T-VEC (Imlygic), for treatment of melanoma. This is the first FDA approval for virotherapy, a new type of cancer treatment that is based a pragmatic therapeutic principle - purposefully modifying a virus so that it can selectively kill malignant cells. My laboratory has employed a novel mechanism to create a HSV-2-based oncolytic virus, the first of this kind (all other oncolytic HSVs, including, T-VEC are constructed from HSV-1). Designated FusOn-H2, it showed potent activity against many tumor types, including breast cancer, pancreatic cancer, ovarian cancer and prostate cancer, when evaluated in a serious of preclinical studies. We discovered recently that this oncolytic virus can actively recruit T cells to the tumor site. In this proposal, we plan to take advantage of this new observation by arming FusOn-H2 with a bi-specific T-cell engager (BiTE) that, when released into the tumor microenvironment, can actively engage the recruited T cells to attack tumor cells.The combined effect of virotherapy (direct killing of tumor cells by the virus) and immunotherapy (destruction of tumor cells by the engaged immune cells) will produce a robust and long-lasting therapeutic benefit. We initially plan to test these strategies in breast cancer. However, this approach can be easily adapted to many other types of cancer such as lung cancer, ovarian cancer, pancreatic cancer and brain tumors. Active efforts are currently under way to translate these novel therapeutic agents into the clinic in the near future, and the proposed studies will benefit patients who are suffering from these malignant diseases with poor prognoses.

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