Replies to post #45688 on OncoSec Medical Inc (ONCSQ)

[Hargrove]

Thanks, "hschlauch"! Your posts often remind me of that old "Management Guru," Tom Peters. He was famous for saying...."There are no excellent companies!" What he meant was....there's no perfect company and top management must always be re-imagining what their product is and what the best version of their product can be. I hope that some ONCS top brass get a chance to tune into this Board and see some of the thoughts expressed about the "micro" environment of their present trials. I think you supply a lot of "re-imagination" food for thought that ONCS senior scientists might want to compile and, at least, consider as the appropriate timeframe and resources permit. The ONCS story is a long way from completion and it's very possible that, if they do continuously "re-imagine" what their BEST product can be, the Company might outlive many of the lives they're on track to help and cure! It's thinking like yours, "hschlauch," that might just help ONCS "re-imagine" what its BEST product can be!


"OXYTOMA HARGROVEI"

[dangerM]

Thanks for emphasizing the following again. It seems I wasn't really understanding it in the full depth before:

The FLT3 ligand then expands the dendritic cell population, thus improving antigen presentation to CD4 and CD8 T cells. Unfortunately, Tregs with their CTLA-4 can control antigen presentation and priming by outcompeting CD80 and CD86 on dendritic cells.

I took this as an occasion to read in some papers which I always wanted to read*.

In short: It seems there is some regulatory feedback between DC and Treg keeping their numbers in balance*. Looking at the feedback loop FLT3L + anti-CTLA4 (and perhaps TGF\beta) would be the most plausible levers to be manipulated in this cycle. I am not certain if both at the same time (due to the possible strength autoimmune reactions), but still.

Probably FLT3L alone is not really hampered because of the temporal delay of any effect on Treg; else Brody could not have produced those interesting mouse data on low-dose radiation with FLT3L which I mentioned here some time ago.

And as well, we know that anti-CTLA4 alone does work.

Again thanks!

dM


* especially this one: Darrasse-Jèze et al (2009), Feedback control of regulatory T cell homeostasis by dendritic cells in vivo

http://jem.rupress.org/content/jem/206/9/1853.full.pdf

Figure 5 on PDF-page 8/page no 1860 of the paper gives some idea, but is a bit much abridged