this is an excerpt from a Publication that Yuman Fong...

this is an excerpt from a Publication that Yuman Fong coauthored, published 2021.
I have a link to this, on a post I will put up, with my thoughts.



The prototype of JX-594 was used in a pilot Phase I trial in 1998 [30]. The virus used was a New York City Board of Health strain of VACV in which the J2R gene was replaced with expression cassettes for hGM-CSF and β-galactosidase. In this study, a total of seven patients with unresectable melanoma were treated twice weekly with intratumoral injections of escalating doses of the virus for 6 weeks. A maximum dose of 8 × 107 PFU virus was used in the study and no maximum tolerable dose (MTD) was reached. Tumor regression in a fraction of patients was observed in this study, and systemic toxicity was limited to flu-like symptoms that resolved within 24 h. Followed by this pilot study, an open-label Phase I dose-escalation trial was conducted with substantially higher doses with the aim of defining safety and the MTD of JX-594 [31]. This study recruited 14 patients with refractory primary or metastatic hepatocellular carcinoma. Patients received intratumoral injection of the virus ranging in doses from 108PFU to 3 × 109 PFU every 3 weeks. Grade 1–3 flu-like symptoms were observed in all patients and 4 out of 14 patients experienced transient grade 1–3 dose-related thrombocytopenia. Furthermore, patients treated with the highest dose (3 × 109 PFU) displayed hyperbilirubinemia, which was considered dose-limiting. From this study, 1 × 109 PFU was determined to be the MTD for JX-594. In addition to finding the MTD, several insights were gained from this Phase I trial. First, the study showed that it is possible for the virus to disseminate from injected to non-injected tumors through blood; virus replication and expression of GM-CSF were also confirmed. Second, tumor responses were observed in both injected and non-injected tumors. In terms of efficacy, out of 10 radiographically evaluable patients, 3 had partial response, 6 had stable disease and 1 had progressive disease.