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Wow!!!! An immune approach to treating all cancer?

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(@jcancom)
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(@daniel)
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Very interesting J. Thank you!


   
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(@jcancom)
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D have you found the exact article from Nature Immunology? 


   
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(@jcancom)
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https://www.nature.com/ni/

https://www.nature.com/articles/s41590-019-0588-6

https://www.nature.com/articles/s41590-019-0578-8

 

One of the articles talks about how this relates to metabolism. Would like to know how.

 


   
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(@daniel)
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@jcancom

I think this is the article (but not in Nature) https://cancerdiscovery.aacrjournals.org/content/early/2019/10/26/2159-8290.CD-19-0569

 


   
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(@jcancom)
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D, actually this is the one. The abstract talks about how this has already been used in melanoma patients?

Is that correct?

https://www.nature.com/articles/s41590-019-0578-8


   
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(@jcancom)
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There are so many millions of desperate cancer patients. The technology that they are discussing seems to be fairly standard. You really wonder whether patients might not just be able to find a route to access this treatment. It is after all thought to be cancer specific.


   
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(@daniel)
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@jcancom

Hi J, I think is the one in Cancer Discovery according to this statement "A journal of the American Association for Cancer Research - Cancer Discovery, has published the findings in a study." and the name of the lead author "Michele Teng" as stated in the first link you posted above (Ref). 

What do you think about this one https://www.nature.com/articles/s43018-019-0018-6 ? I think it's very interesting.


   
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(@jcancom)
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D, you know what would be extremely cool? If they screened the entire CAS numbers! 3-BP just popped out of nowhere. What would happen if they just went ahead and essentially screened ALL known chemicals. That would be super exciting! They could be completely agnostic. Who knows what they might find.


   
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(@jcancom)
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I will expand upon my previous comment (especially as I received a D like! on it) . I think that there is too much emphasis on the brilliant scientist meme and not enough on the crank up the machine and try all options meme. When I look back on many science breakthroughs (e.g., 3-BP) I am constantly amazed that the idea had never been thought of before. There are a whole bunch of halogen chemicals DCA, 3-BP etc with anti- cancer effect. It is difficult for me to believe that a chemical that looked a whole bunch like lactate and a great many similar chemicals with a big bromine atom at the front would not have strong anti-cancer effects. Instead of over-thinking things why not just turn  on the chem robot and let it run for a while. There must be so many discoveries out there that could be found by simply searching every possible combination.

This also seems to happen often with disease risk factors. Scientists stumble upon drug X just happening to help with condition Y. These are trickier because often there is no obvious reason why there would be such connections. Why aren't supercomputers working away 24/7 on every possible combination with all the data that exists? Who knows what weirdness that they might be able to turn up? As it is now weirdness does turn up sooner or later, though it always seems to be a chance meeting of two synapses; using the massive power of computer chips one could systemically isolate such discoveries with precision. Perhaps one could essentially search the entire space of possibilities and have a complete solution of what could be found.      


   
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(@daniel)
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Posted by: @jcancom

D, actually this is the one. The abstract talks about how this has already been used in melanoma patients?

Is that correct?

https://www.nature.com/articles/s41590-019-0578-8

J, I was reading some news and came across this article. Next I realise that this may be the one you intended to post at the beginning of this thread which is indeed different compared to the first one you posted. Here are the news I was reading https://www.cardiff.ac.uk/news/view/1749599-discovery-of-new-t-cell-raises-prospect-of-universal-cancer-therapy

These are really great news!


   
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(@asafsh)
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@daniel

Yes, this is a great news. But CAR-T cost ... unconfirmed up to 400K . Not many can afford this price. 


   
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(@jcancom)
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D, it surprises me how many differences exist between cancer and normal cells. The dogma has always been that curing cancer is sooo tough because cancer cells are so similar to normal cells. Yet after all of these years we have seen a great number of examples in which cancer cells are very different from normal cells. This latest research is possibly one of the most glaring differences to date. Are they saying that there is an immune receptor on cancer cells that recognized by T-cells that is different? I am often quite surprised by the discoveries in science, not so much that the discovery is surprising but instead that what had been discovered had not been discovered before. Perhaps they could somehow do an agnostic scan of all the receptors and other channels on the surface of cancer cells that might be different from normal cells. Would be great to have a comprehensive analysis.    


   
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(@jcancom)
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asafsh, I am wondering whether it might be possible to develop an off-the-shelf product using this research. If they could possibly develop a universal MR-1 T-cell, then the cost might be enormously reduced.


   
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(@daniel)
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@jcancom

I am also wondering if this could become faster accessible to humans J, as based on their statements it seems they expect a possible go to market in a few year, which indicates that the manufacturing may not be that complex?


   
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(@daniel)
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@asafsh

Yes asafsh. That's huge. Let's hope cheaper options will become available. And there is hope for that. As technology advances and is widely adopted, the related solutions are naturally becoming cheaper.


   
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(@marcosbomber901)
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(@manuone)
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@marcosbomber901

Hi Marcos!

A very interesting article! . Unfortunately I am finding limitations with the use of 2 dg. It seems that after more than a year and a half my mother does not tolerate it well. There may be some problem with the QT interval promoted with the use of antibiotics (doxycycline and salinomycin).
Daniel suggests that I only use 1 g in 48 hours but I don't know if this will avoid the problem because the amount administered during these hours has been proportionally similar ... I hope that he recovers well and can draw better conclusions.
It would be a shame not to be able to use 2 DGs again in therapy.

regards


   
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(@dumbcritic)
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@jcancom

One company is using healthy (T) cells from donors. They screen for different phenotypes, including for exhaustion and senescent markers, both before engineering and after production, as well as for T-cell subsets. The products produced should be more potent [1] and consistent. It also allows for broader access and flexible dosing (e.g., re-dosing).

The first CAR will be against CD70. The highest expression is in RCC, but many types express it [2,3].

Improved versions will avoid exhaustion, modulate immunosuppressive TMEs, recruit endogenous immunity, have logic gates and much more. Here is some early data [4].

Based on this it may only be a matter of time before MR1 is targeted.

However, the downside is HvG, but there are a number of ways to address this, such as this [5].

Refs:
1 https://crisprtx.gcs-web.com/static-files/bca61f6d-452c-4523-bc90-99605f616893
2 https://www.nature.com/articles/6605816
3 https://www.tandfonline.com/doi/full/10.1517/14728222.12.3.341
4 https://crisprtx.gcs-web.com/static-files/8ea0746a-7aaf-4350-a451-db66efa26f6b
5 https://www.sciencedirect.com/science/article/abs/pii/S0041134506014060


   
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(@asafsh)
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@jcancom

it is difficult for me to answer this question as my background is quite outside of medicine or biomolecular research fields. The price information i got while searching for possible treatments for my close relative i am trying to save right now.

Perhaps, approach mentioned by dumbcritic is the easiest one. possibly this approach ((i can't confirm or validate this) was inspired by Zheng Cui's (there is a topic here on his another work on garlic injection) work dated back to 1999 when mice immune to cancer cells were discovered:

White Blood Cells From Cancer-resistant Mice Cure Cancers In Ordinary Mice

"The cancer-resistant mice all stem from a single mouse discovered in 1999. "The cancer resistance trait so far has been passed to more than 2,000 descendants in 14 generations," said Cui, associate professor of pathology. It also has been bred into three additional mouse strains. About 40 percent of each generation inherits the protection from cancer."

Rumors are Mr. Zheng Cui was able to cure his wife by simple blood transfusion.

Then, approximating murine model to human as if cancer resistance is preserved through generations then it should be easy to pre-screen probably healthy donors by evaluating medical history of their descendants and refine the list in lab then. 

It shouldn't be difficult to start such initiative from ground through universities.

I have tried to contact him for garlic injections, but he left Wake Forest University few years ago. 


   
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(@asafsh)
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@daniel

Daniel, sure, i agree with you. The competition is a main driver in today's world. The only problem money. Big money. 

Ironically, in USA, FDA welcomes cheaper treatment alternatives while R&D/supply/production costs are exaggerated by its own regulations. What we have at the end - there is not much place left for small dynamic companies that wish to develop cheap alternatives, as financially it is very difficult for such companies to take products from idea to the production. Most probably these companies are consumed by larger major players. 

And i know how these big TNC work. Majority shareholders will put constrains on headquarters to generate a profit and growth. headquarters are profit oriented yet because of bonus system. From that perspective, they will favor targeting drugs that extend life by few months instead of putting money into fundamental and multi-years research to get something useful at the end. said is not a conspiracy theory, it is how the system works.

So it seems ReDo is the only one of few alternatives that can possibly survive and put pressure on major players. 


   
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(@darlebeinnein-com)
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@asafsh Has the possibility of crowd funding the trials needed to get the most promising redo drugs accepted for treatment. Possibly working on a few at a time would get it started.

 


   
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