Grant: Project Grant

Oncolytic viruses (OV) are emerging as an exciting platform for successful cancer immunotherapy due to their potential for long-lasting efficacy with minimal adverse side effects. Currently approved OVs are restricted to direct delivery to accessible tumors, which causes patient discomfort and limits targeting of non-accessible or metastatic tumors. One perceived barrier of intravenous (IV) delivery is neutralization of the virus by circulating antibodies. These antibodies are naturally produced as a response to virus detection to protect against subsequent infection (as with vaccination). While OV treatment produces antibodies such as neutralizing antibodies, emerging data from several labs, including ours, suggest that neutralizing antibodies may actually be of benefit. These observations highlight that the underlying mechanisms of OV administration and activity are not fully understood. The goal of this project is to further understand the effects of generated antibodies, including neutralizing antibodies, and other aspects of immunity on systemically delivered OVs. For these studies, we will use three different cancer types and three different anatomic locations. As systemic administration enables targeting of distal and metastatic tumors, is easier to perform and limits patient discomfort, understanding IV administration will ensure that we realize the full potential of OV-based immunotherapy, ultimately improving patient care by enabling treatment of hard-to-reach metastases or tumors inaccessible by surgery and allowing OV cancer treatment to be more tolerable and more accessible in regions where surgical resources and affiliated expertise are scarce.