RE:RE:RE:RE:RE:SORT vs Other targeting PlatformsAgain, all this VM inhibition is a consquence of the endocytosis that happen when the peptide-drug conjugate interact with Sort1 receptors. It is the activation of Sort1 endocytosis that lead to VM inhibition, and only in advannced metastatic tumour exhibiting the VM process. My understanding is that VM occurs only in advanced invasive metastatic cancers. I see it as an added benefit, not the main feature. The main feature is concentrating a highly cytotoxic drug inside cancer cells that are overexpressing the Sort1 receptor to kill them. Again, it's only my understanding. I should add that even Thera seems to not understand exactly how the VM inhibition works on a biomolecular basis.
juniper88 wrote: I was trying to say that the target is CD133. The sortilin receptor is the target. But it turns out that the cells being destroyed (and have the sortilin receptor) are cells that have CD133. So, TH-1902 is potentially destroying Cancer Stem Cells and cells involved in VM. STO-002 is not. To me that might be a big difference in the long term prognosis of the patient. But I could be completely misunderstanding that.
qwerty22 wrote: When tumours employ vasculogenic mimicry essentially what is happening is some cells are activated to change their structural characteristic so they can form vessels by binding to their neighbour cells in a different way. One change is to express cd133 on the surface. In thtx's expt they just use cd133 as a marker of VM so they can stain and highlight those cells on a slide and see what is happening. There is no "targeting" of cd133, cd133 is just being used as a visualization tool. If there is no VM then there is no cd133, if the drug inhibits VM then there is no cd133 to visualize. It's a practical tool the scientists are using not a target for the drug.
jfm1330 wrote: TH-1902 targets cells with Sortilin receptors, if there is also vasculomimicry linked to CD133 expression, it will inhibit that, but my understanding is that it is a secondary effect of the endocytosis of TH-1903 linked to the Sortilin 1 receptor. So the primary target is really the Sortiliin 1 receptor to get the drug inside the cell, and the primary goal is to kill the cancer cell with docetaxel, vasulomimicry inhibition is just an added benifit in some agressive metastatic cancers. That's my understanding, maybe I missed something.
juniper88 wrote: From the press releases that I have seen from Sutro and Thera, I see 3 differences. I can't comment how TH-1902 differences with STRO-002 would also apply to other 'smart bomb' cancer platforms.
1) The target. STRO-002 goes after cells that have CD74 expressed whereas TH-1902 goes after cells with CD133. To me this is the biggest difference, becausefrom what I have read CD133 is used to identify Cancer Stem Cells, which are the cancer cell that are resistant to conventional chemo drugs. If TH-1902 can wipe those out that would be a very big deal.
2) The method. Using a peptide instead of an antibody. Peptides are much smaller than antibodies. Perhaps that can give a peptide an advantage ?
3) The payload. TH-1902 uses a well know cytotoxic drug, docetaxol whereas STRO-002 uses an unproven proprietory drug. Taxol came out of a project in the 70's that aimed to identify the most lethal cytotoxic naturally derived substance. The scientist came up with taxol that came from the Pacific Yew. The one drawback of taxol was the side effects it caused and was almost not approved.
What stands out with me with STR-002 is that it managed to get stable disease for 74% of patients by week 12, but that rapidly fell off. It possibly killed off cells with CD74 but then other cells not affected by STR-002 took over, in particular cells with CD133 that are responsible for metastasis and vascularization.
realitycheck4u wrote: Anyone care to provide a synopsis on how SORT is like and unlike both 'smart bomb' cancer 'cells targeting platforms and those which use a marker to better allow other drugs to become more affective so they are more effective. Then maybe why SORT is unique. I'd like that if possible. Thanks