RE:RE:RE:RE:RE:To better understand the complexity of ADCsSo here is the link to the full article about PDCs. The only approved one is Lutathera, which was the source of my enthusiasm for this approach used by Thera in SORT1+. That being said, Lutathera is a peptide linked to a radioisotope. The linker is stable and no cleavage within the cell is needed for cytotoxic activity. No PDCs carrying chemotherapy drugs have been approved yet, only ADCs were able to achieve that as of now.
Reading the article and understanding it allow to realize that success of a PDC is linked to many factors. First you need a peptide with high affinity with an overexpressed receptor on cancer cells and low expression elsewhere in healthy tissues. This affinity needs to be preserved after the linkage of one or many drug molecules to the peptide. The peptide also need to allow such linkage of drug molecule. The linker used need to be stable in the bloodstream and outside of cancer cells, but cleavable once inside the cancer cell. The peptide itself need to be stable enough in the blodstream and preserve its structural integrity long enough to have the time to interact with its receptor. So this process involves peptide stability and whole PDC stability, and a fast rate of cell penetration, fast enough to alloe drug internalization before peptide degradation by proteolytic enzymes.
One thing that seems to distinguishes Thera's PDC is the vasculomimicry inhibition. I did not read anything similar about other PDC. It would be the only PDC with a possible added anti-cancer activity. We know that Somatostatin analogs like Octreotide or (Tyr3) Octreotide, used in Lutathera, have antiproliferative activity, but only if the dose is sustained over a long time by daily injections of Octreotide or by monthly injections of a long acting version of Octreotide called Sandostatin (LAR), but nothing linked to Lutathera itself, since it is in the bloodstream only for a few hours. That being said, this vasculomimicry inhibition would need to be proven in humans, but if real, maybe in the future they could devise a drug based only on that.
So all that to say that a successful PDC would require a lot of things to be right at the same time. It seems from what we know now that Thera has a good PDC candidate. It works in xenograft animal models. Now its time for the real test in human. I hope the linker is right and that in some ways they will be able to select patients with cancers that are really overexpressing the Sortilin receptor, because without that, as good as the PDC can be, success is impossible. The whole thing is based on Sortilin receptor overexpression.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7359416/
jfm1330 wrote: From the same article again. On the importance for Thera to developp asap their peptide coupled with Ga68. It is a common thing in this field an easy to do. Look.
More than 200 reports were published focusing on the investigation of various Bn-like peptides conjugated primarily with radionuclides, including 9mTc, 111In, 67Ga, 68Ga, 64Cu, 177Lu, 90Y or 213Bi, which were either used for tumor diagnostic or peptide receptor radionuclide therapy (PRRT) (Dash et al., 2015).
A number of these studies reported excellent visualization of BnR overexpressing tumors like prostate cancer in vivo as well as in humans (Scopinaro et al., 2002, 2004; van Essen et al., 2009).