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On number 3 it’s Immune Checkpoint Inhibitors are also called Checkpoint inhibitors it’s about PD-L1, number 4 is about chemotherapy and synthetic small molecules ie PARP/Chk1/Wee1/ATR!
“T Cell Checkpoint Inhibitors. In a similar way that CD47 on cancer cells suppresses macrophages, some cancer cells can suppress T cell attacks by expressing immune checkpoint proteins such as PD-L1. This can reduce the potency of the specific anti-cancer T cell responses that macrophages mobilize after ingesting cancer cells. Combining our magrolimab immunotherapy with T cell checkpoint inhibitors may help maximize the T cell response induced by macrophages.”
Sorry Potnak can’t see anything on that page was looking at it earlier!
There is an image here https://www.fortyseveninc.com/science#CD47
Where it says amplifies the efficacy of CHK1 inhibitors.
There is an image here https://www.fortyseveninc.com/science#CD47
Where it says amplifies the efficacy of CHK1 inhibitors.
Potnak is there info that it could enhance chk1 think I’ve missed something here, Thankyou?
For me, it's too big a coincidence that Gilead are trying to buy a company that is developing a compound that could enhance the efficacy of CHK1 inhibitors which they also have a stake in. We'll have to see how this pans out but I believe we have our (or sierra does) funding for SRA737. And The quicker we get to a milestone trigger the better.
There never is a direct correlation to the answer with surmising/postulating looking at research and looking at the company’s that matter what they are trying to achieve, trying to figure out what the hell is going on, only they know or the academics until Sierra actually comes out tells us directly and says they are advancing SRA737 then at that point only can we be happy, what ever they are doing is certainly taking a fair bit of time, last June to be looking for undillutive alliances, whether it’s Gilead and trying to keep everything in house as not to loose a cut a big slice out of the 737 pie!
Hi all. Stupid question what does this all mean? Is this good or bad news for our chk1? Most of this goes above my head. Keep up the good research
So is SRA737/LDG creating a similar environment that the CD47 inhibitor would be doing to pair with a PD-L1/CTLA-4, or is it a mechanism that can be synergies, or another armament in the toolbox to kill cancer?
“activate more Macrophages could be a rationale!”
change to :-
“activate the increased population Macrophages could be a rationale!”
The rumor of Gilead taking over 47 inc tells me that Gilead wants to sure up their oncology portfolio, so that’s the positive I’m going to take here!
What is 47’s Anti CD47 Antibody and what does it do?
Magrolimab is an antibody designed to block the CD47 “don’t eat me” signal, restoring the ability of macrophages to attack and destroy cancer and the balance towards phagocytosis (the macrophages engulf and kills cancer cells)
Is there any rational for the combination of 47’s CD47 inhibitor and SRA737 in a mechanism for combining, we know that a PD-L1 with SRA737/LDG in mouse models at the MD Anderson is a known potential route forward in SCLC in the clinic as SRA737 initiates the STING pathway the interferon signaling and immune system activation which (increases M1 Macrophages (antitumor) decreases M2 Macrophages (Protumor)) and looks as if SRA737 and LDG highlights to the immune system where the cancer is in SCLC, or is it the same as cancelling the “don’t eat me signal” and preventing cancer from suppressing the innate immune system!
Only a thought in relationships with “Combination treatment of the oral CHK1 inhibitor, SRA737 and low dose gemcitabine, enhances the effect of PD-L1 blockade by modulating the immune microenvironment in small cell lung cancer.” it could be that maybe because SRA737/LDG recruits more good M1 Macrophages, then maybe the mechanism of producing more Macrophages and also the impact of turning off CD47 to activate more Macrophages could be a rationale!
Another rationale is the below statement from T.Sen with enhanced T-cell infiltration and there is research to show that the CD47 inhibition needs the T-cells that are required for anti-CD47 induced regression!
“We observed that the combination of LDG+SRA737+anti-PD-L1 leads to enhanced T-cell infiltration with coincident decrease of T-cell exhaustion”
And also:-
“We further show that combining low dose non-cytotoxic gemcitabine, a known RS-inducing agent, with SRA737+anti-PD-L1 can significantly increase anti-tumorigenic CD8+ cytotoxic T-cell, dendritic cell and M1 macrophage populations. Also, the regimen led to significant decrease in immunosuppressive M2 macrophage and MDSC populations in an SCLC model.”
Research to show that the CD47 inhibition needs the CD8+T-cells!
The Antitumor Activity of CD47 Blockade Depends on T-cell Activation :-
“Colleagues treated both immunocompetent and T cell–deficient mice bearing immunogenic syngeneic tumors with a CD47-blocking antibody and observed tumor regression only in immunocompetent mice, but not when CD8+ T cells were depleted, indicating that an antigen-specific CD8+ T-cell response is required for the antitumor activity of CD47 blockade.”
https://cancerdiscovery.aacrjournals.org/content/early/2015/09/09/2159-8290.CD-RW2015-172
So is SRA737/LDG creating a similar environment that CD47 inhibitor would be doing to pair with a PD-L1/CTLA-4, or a mechanism that can be synergies, or anot
Amplifies the efficacy of checkpoint inhibitors.