Facilitating Repeat Intracarotid Injections in Mouse Models by a Novel Injection Site Repair Technique

Our research focuses on developing novel biological therapies for glioblastoma, including agents such as oncolytic viruses, and microRNAs. A major reason why brain tumor therapeutics fail, is ineffective delivery to the tumor within the brain. So we focus on developing new delivery methods, including mesenchymal stem cells and exosomes, which can be delivered by intra-arterial injection.

Oncolytic viruses and immune cell therapies such as CAR T-cells and NK cells, have shown great promise in vitro, but delivery to tumors in vivo remains challenging. We have established a clinical endovascular neurosurgical oncology program, which is complemented by basic and translational research approaches that focus on intra-arterial delivery of brain tumor therapeutics. One of the biggest challenges is effectively delivering therapies to brain tumors.

Intratumoral delivery has been used with some agents, but has had limited success because re-injection is not feasible and the agent may not reach all parts of the tumor. We are addressing this issue through intra-arterial delivery of therapeutics. Previous methods of injection through the carotid artery have employed ligation of the injected artery, and resulted in ischemic stroke in some mouse models that do not have a complete circle of Willis.

We developed a method to repair the injection site, preventing this issue, and enabling subsequent re-injection within the same artery. For brain tumors, we will continue to develop mesenchymal stem cells as delivery vehicles for oncolytic viruses and exosomes to deliver therapeutic cargoes, including microRNAs. It is important to note that with both of these agents, intra-arterial injection is key to efficient delivery and therapeutic benefit.