Of course, intratumoral will give the most bang for the buck versus intravenous. Still, plenty of evidence suggests CF33 with and without a transgene travels through the bloodstream and attacks distant tumours. The virus replicates only in tumours and causes inflammation which elicits an immune response then, once it tumour bursts CF33 virus enters the bloodstream, CF33 has been found even to attack distant peritoneal tumours after under-skin intratumoral injections. Both the studies below state that distant i.e. not injected tumours, have benefited from CF33. A benefit derived solely from CF33's ability to travel in the host's bloodstream.
PET imaging and treatment of pancreatic cancer peritoneal carcinomatosis after subcutaneous intratumoral administration of a novel oncolytic virus, CF33-hNIS-antiPDL1CF33-hNIS-antiPDL1 replicates in locally injected and
distally located tumors to express functional hNIS protein
Novel oncolytic chimeric orthopoxvirus causes regression of pancreatic cancer xenografts and exhibits abscopal effect at a single low dose
In both of the above they waited for subcutaneous (under the skin) and distant peritoneal tumours to grow to 100m3 before treatment.
We observed a continued decrease in the peritoneal tumor burden in the CF33-hNIS-antiPDL1-treated group throughout sequential imaging of the animals. In contrast, the unchecked tumor growth in the control group led to the death of all of the animals. As measured by bioluminescence imaging, the greatest difference in the peritoneal tumor burden between the 2 groups was demonstrated at day 14 (p < 0.05; Figure 6). Six surviving mice in the CF33-hNIS-antiPDL1-treated group showed further decreased peritoneal tumor burden at 28 days compared to 14 days, as well as to the only surviving mouse in the control group. By day 217, the 2 surviving mice in the CF33-hNIS-antiPDL1-treated group showed complete remission of their PC (Figure 6). These data suggest that i.t. CF33-hNIS-antiPDL1 administration of s.c. tumors affects peritoneal tumors within 14 days, and this therapeutic efficacy leads to both complete remission and improved survival.The above states that the 'distant' i.e. not injected tumours had high levels of CF33 and therapeutic benefit. All of which suggests that CF33 will be beneficial intravenously. Will tumours injected directly benefit more than those that aren't? Yes. Are all tumours in a person's body accessible? Unfortunately not. Hence the significance of the peritoneal study. Metastasis in this area in humans is usually fatal in part due to them being unresectable (inoperable). So in the study results for Vaxinia will be interesting, given it is a more robust version of Checkvacc, potentially spending more time in the body to hunt down tumours. One other thing important to note is the therapeutic window CF33 has. 1000 particles in mice were curative and 1 billion was deadly. This is significant because if CF33 is shown to attack distant tumours and be efficacious to any extent, there is plenty of room to increase the dosage to have enough CF33 in the bloodstream to attack all cancers.
The above preclinical studies seem very promising and suggest CF33 can certainly be successful in humans. Yuman Fong mentioned that they are seeing exactly what they say in mice trials (above) in humans. That was a few weeks ago, AFTER IMU had dosed 3 cohorts in the IV arm. Its certainly yet to be a slam-dunk. But it's certainly looking very promising.
Don't take my word for it, though. If anyone is interested, I have a few audio snippets from the man himself. There's also a short mention of current OV's compared to CF33, highlighting its potential for greater success.
http://sndup.net/dz7n
(20min delay)
