Development of a novel stem-cell based carrier for intravenous delivery of oncolytic viruses

Cytonus Therapeutics has developed an innovative, precision delivery platform that brings biologically active therapeutics to the anatomical niches where metastatic cancer cells thrive. Cytonus delivery platform centers on the use of CargocytesTM, which are biomimetics devoid of genomic DNA and engineered from cellular materials with tissue precise homing molecules that promote specific tissue targeting and penetration. Because Cargocytes are energetically, morphologically, and biosynthetically active they can deliver therapeutic payloads to primary and secondary tumor, where they retain the ability to effectively synthesize and secrete therapeutic proteins, generating a highly localized effect and minimal systemic toxicity. In this CIRM Discovery award, we have evaluated the ability of a Cargocyte to deliver oncolytic viruses (OVs) in a mouse model of metastatic cancer. While OVs have shown great promise as a cancer therapy their successful use in the clinic has been hindered by their failure to access solid tumors when administered systemically, resulting in ineffective antitumor efficacy. Here, we show that Cargocyte-mediated delivery of OVs results in localized viral replication and solid tumor cell killing in mice. Specifically, we demonstrate that systemically administered Cargocytes loaded with OVs effectively home to and extravasate from the blood and replicate within the tumor and not in healthy non-tumor target tissue. This result is in contrast to systemically administered naked OVs, which are retained in the blood and consequently replicate broadly in non-target tissues. These findings support the idea that the Cargocyte platform can effectively and precisely deliver biological therapeutics into the tumor microenvironment. This CIRM award facilitated the development of the Cargocyte platform, using OVs as a therapeutic cargo in the fight against cancer.