Why Armored CAR T Therapy Is Our Best Shot At Curing Cancer (thedailybeast.com) 40
An anonymous reader quotes a report from Ars Technica: Immune therapies have rewritten the game when it comes to cancer treatment, earning the "fifth pillar" label next to more tried and true treatments like radiation therapy, surgery, and chemotherapy. And no immunotherapy has garnered quite the same excitement as CAR T-cell therapy, first approved in 2017 by the Food and Drug Administration to treat a form of acute lymphoblastic leukemia. At the time, then-FDA Commissioner Scott Gottlieb called the approval "a new frontier in medical innovation," and it seemed like the possibilities for CAR T were near-endless. Flash-forward almost six years, and six therapies have been approved for blood cancers, including lymphomas, leukemia, and multiple myeloma. There's no question that when CAR T works, it works incredibly well. But why it doesn't work for the majority of patients or cancer types has befuddled researchers.
CAR T therapies also haven't yet been expanded to treat solid tumors, which make up the majority of cancers. The immune therapy hasn't been able to crack physical barriers, idiosyncratic tumor cells, and a suppressive microenvironment that characterize these cancers. But a new generation of CAR T therapies are emerging, equipped with highly effective small molecules that scientists hope will solve their low success rate for both blood cancers and solid tumors. Known as "armored CAR T," these infusions have been boosted with additional layers of protection and cancer-fighting proteins. Early research shows that the armored flavor of CAR T might have what it takes for immunotherapy to go the extra mile.
Briefly, immunotherapy can boost or restore the body's immune system by lowering cancer cells' defenses, priming the immune system's T cells to destroy tumors, or -- in the case of CAR T-cell therapy -- genetically editing a patient's T cells. Scientists do this by isolating a patient's T cells from their blood and inserting a gene for a chimeric antigen receptor -- a type of synthetic protein that has been specially made to bind to another protein present on the surface of that patient's cancer cells. Then, upon infusing these modified T cells back into a patient, the immune fighters will recognize and destroy the tumor cells when the patient's normal T cells have failed. That, at least, is the idea. But when CAR T doesn't work, a few factors could be at play. One, Lim said, is the tumor microenvironment, the set of chemicals and structures present in solid cancers that naturally suppress pushback from the body's immune system. Tumor heterogeneity is also a factor -- depending on the type and stage of cancer, tumor cells may not express the protein that the CAR T cells' receptors have been designed to recognize, blocking the ability of the CAR T cells to attack the cancer Finally, there are physical barriers on the outside of a solid tumor that can even prevent the T cells from entering inside to destroy the cancer. Armored CAR T is meant to overcome these difficulties. With this form of therapy, not only are T cells engineered to express a tumor cell's surface protein, they are also given potent cargo often in the form of small proteins called cytokines. If deployed on their own, such molecules can be toxic -- but pairing them with T cells designed to release them at the tumor site and nowhere else represents a promising new strategy. Jakub Svodoba, an oncologist at the University of Pennsylvania, "is helping to lead a clinical trial using armored CAR T-cell therapy to treat patients with non-Hodgkin lymphoma for whom previous CAR T therapy has failed," reports the Daily Beast. "Last month, he presented findings that the first seven patients treated with this therapy all responded to it and were alive eight months after receiving it. Svoboda said an important additional finding was that toxicities experienced by the patients -- a concern with cytokines -- were comparable to those from traditional CAR T therapy."
Wendell Lim, a cellular and molecular pharmacology researcher at the University of California, San Francisco, and his team are also working on an armored CAR-T therapy, with the potential for it to be used to treat solid tumors. "In a paper published in Science on Dec. 16, he and his colleagues designed T cells to release a cytokine directly to the tumors of mice with pancreatic cancer and melanoma," reports the Daily Beast. "In the study, they wrote that these cancers are 'nearly completely resistant' to treatment with traditional CAR T, but releasing a cytokine allowed the engineered T cells to get past the tumor microenvironment -- effectively solving one of the issues that has set the therapy back."
CAR T therapies also haven't yet been expanded to treat solid tumors, which make up the majority of cancers. The immune therapy hasn't been able to crack physical barriers, idiosyncratic tumor cells, and a suppressive microenvironment that characterize these cancers. But a new generation of CAR T therapies are emerging, equipped with highly effective small molecules that scientists hope will solve their low success rate for both blood cancers and solid tumors. Known as "armored CAR T," these infusions have been boosted with additional layers of protection and cancer-fighting proteins. Early research shows that the armored flavor of CAR T might have what it takes for immunotherapy to go the extra mile.
Briefly, immunotherapy can boost or restore the body's immune system by lowering cancer cells' defenses, priming the immune system's T cells to destroy tumors, or -- in the case of CAR T-cell therapy -- genetically editing a patient's T cells. Scientists do this by isolating a patient's T cells from their blood and inserting a gene for a chimeric antigen receptor -- a type of synthetic protein that has been specially made to bind to another protein present on the surface of that patient's cancer cells. Then, upon infusing these modified T cells back into a patient, the immune fighters will recognize and destroy the tumor cells when the patient's normal T cells have failed. That, at least, is the idea. But when CAR T doesn't work, a few factors could be at play. One, Lim said, is the tumor microenvironment, the set of chemicals and structures present in solid cancers that naturally suppress pushback from the body's immune system. Tumor heterogeneity is also a factor -- depending on the type and stage of cancer, tumor cells may not express the protein that the CAR T cells' receptors have been designed to recognize, blocking the ability of the CAR T cells to attack the cancer Finally, there are physical barriers on the outside of a solid tumor that can even prevent the T cells from entering inside to destroy the cancer. Armored CAR T is meant to overcome these difficulties. With this form of therapy, not only are T cells engineered to express a tumor cell's surface protein, they are also given potent cargo often in the form of small proteins called cytokines. If deployed on their own, such molecules can be toxic -- but pairing them with T cells designed to release them at the tumor site and nowhere else represents a promising new strategy. Jakub Svodoba, an oncologist at the University of Pennsylvania, "is helping to lead a clinical trial using armored CAR T-cell therapy to treat patients with non-Hodgkin lymphoma for whom previous CAR T therapy has failed," reports the Daily Beast. "Last month, he presented findings that the first seven patients treated with this therapy all responded to it and were alive eight months after receiving it. Svoboda said an important additional finding was that toxicities experienced by the patients -- a concern with cytokines -- were comparable to those from traditional CAR T therapy."
Wendell Lim, a cellular and molecular pharmacology researcher at the University of California, San Francisco, and his team are also working on an armored CAR-T therapy, with the potential for it to be used to treat solid tumors. "In a paper published in Science on Dec. 16, he and his colleagues designed T cells to release a cytokine directly to the tumors of mice with pancreatic cancer and melanoma," reports the Daily Beast. "In the study, they wrote that these cancers are 'nearly completely resistant' to treatment with traditional CAR T, but releasing a cytokine allowed the engineered T cells to get past the tumor microenvironment -- effectively solving one of the issues that has set the therapy back."
TypeSSS (Score:4, Informative)
But why it doesn't work for the majority of patients or cancer types has befuddled researchers.
The answer is right there in the question. "Types". Cancer isn't a single, monolithic thing. It's lots of different types of cancer and not just "brain cancer" and "colon cancer" types. There are different types of brain cancers and colon cancers and on and on. To think that there's going to be a single magic bullet that cures all cancers shows a lack of understanding of the scope of the problem(s).
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It depends, the magic bullet itself can work if it's programmable. That's where cancer treatment is evolving too. The bullet is programmed with the signature(s) of the cancer and destroys it. I'm of course oversimplifying it. But think of it this way, you can't say that we cannot catch bank robbers because every bank robber has a unique look and a unique residence? Well fact is that it doesn't matter, because we have a police, a system for arresting fugitives. The FBI can get a picture of their face, run fa
Re: TypeSSS (Score:2)
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One of these days. Hopefully before I die of old age.
Re: TypeSSS (Score:2)
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To think that there's going to be a single magic bullet that cures all cancers shows a lack of understanding of the scope of the problem(s).
There are similarities. All cancers have drastically defective genomes. There are also other similarities, for example, every cancer damages the P53 gene pathway in some way or another. (If it didn't, the cell would recognize the DNA was damaged and perform apoptosis instead of multiplying).
There has been some work on recognizing cells with defective P53 genes as a way to destroy all cancers, but it hasn't yielded results yet. There are a lot of exciting things coming down the pipeline.
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But why it doesn't work for the majority of patients or cancer types has befuddled researchers.
The answer is right there in the question. "Types". Cancer isn't a single, monolithic thing. It's lots of different types of cancer and not just "brain cancer" and "colon cancer" types. There are different types of brain cancers and colon cancers and on and on. To think that there's going to be a single magic bullet that cures all cancers shows a lack of understanding of the scope of the problem(s).
There’s more to it than that, though. IIRC, some hard tumors end up with a layer of biofilm (bacteria, etc.) that hides the cancer from the immune system. Something about creating a highly acidic environment around the tumor ends up preventing normal immune function. I forget the details.
The lack of consistent tumor markers in some tumors is also a problem; the immune system can’t attack something that just looks like normal cells.
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Gee, if only the people who are literally editing genomes to attack a specific cancer knew that every cancer was different.
You should write a paper.
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If you reason that cancer is not really a single thing, you have to apply that same reasoning to immune therapy too: it's not a single thing either. While you could say the same for chemotherapy, it's not a single thing either, but immune therapy exploits a single system that is ubiquitous in the human body -- the immune system.
This doesn't mean that a successful immune treatment for one kind of cancer means we can treat *all* kinds of cancer, but it's a step in that direction. It's probably not surprisi
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Getting immune therapy to work in the brain may be a challenge, but once you crack that you have a pretty good chance of seeing progress on multiple kinds of brain cancers.
That may also depend on what you mean by "immune". Presumably antibodies could be delivered directly into the cerebrospinal fluid. T cells, perhaps not.
Uh no.. (Score:4, Interesting)
It's not our best shot, not even by a long shot. There are a lot more promising technologies in the pipeline, that I've seen showing good results in the labs. For one thing, CAR T-cell technology relies on the cancer being stupid enough to display the same unique antigens on its surface. That's like a rookie mistake, how many stage IV cancers are that dumb? Luckily quite a few are, but eventually many tumors wisen up and many of tumors either don't display the targeted antigens or even worse don't display anything that enables efficient targeting.
There are instead better approaches, one, for example involves interrogating the interior of the cell and activating on DNA or RNA (using cas12 and cas13 type proteins -- and some others that not worth mentioning.) The point is that we're developing solutions against cancer that don't work off the surface of the cancer cell, but rather act directly inside the cell where the mutations that define a cell as cancerous sit. Of course these are still in the early stage of development, there is a LOT of work to be done (improving the therapeutic's efficient entry into all types of cells, ensuring efficiency of activity in all cell conditions, efflux evasion, zero or very low off-target triggering etc.).
Re: Uh no.. (Score:2)
As a pharma guy, I want a cure. Because it will allow me to simply buy up the competition from the profits over the patent period alone. Also, it will mean I get a Nobel prize when I'm the lead scientist on the discovery. Not something a scientist will ignore for money, because if I'm the lead scientist I will already have plenty of money.
Re: Uh no.. (Score:1)
CAR-T is just too expensive (Score:5, Insightful)
The problem is scale; it's unachievable in it's current form. CAR-T costs between $1M per patient. That's because even similarly classified cancers are still different for every patient. You have to train the patient's T-cells to recognize and destroy their cancer, and given that every patient is unique there is no way to scale that process; each patient is it's own discovery process.
We all like to think that no one should have to pay for healthcare, but the reality is someone has to. In 2022 there were 1.9 million new cases of cancer. At $1M to cure each one, you're talking $1.9 trillion dollars, per year, to eradicate cancer with CAR-T. It's simply unaffordable except as a last ditch effort; it will always be a therapy of last resort unless new bioreactors come on line that can automate the training of CAR-T to each patient uniquely, which requires new biosensing techniques to automate the training process that we simply don't have.
Science is great to show potential, but deployment is a logistics issue, and CAR-T is just too expensive to be real other than a last choice solution. It could be scaled, but there's no one really working on these kinds of technologies so no telling when that will happen.
Bound to Improve (Score:2)
In 2022 there were 1.9 million new cases of cancer. At $1M to cure each one, you're talking $1.9 trillion dollars, per year
First, that's not entirely fair since many cancers already have good prognoses so many of these cases can be treated by existing methods leaving the more expensive approach for those that either have no good treatment option or that have failed to respond to existing treatments.
Second, while every patient may be unique that does not mean that we cannot develop common processes to cope with our uniqueness. For example, everyone used to have clothes that were made to measure until we found it was much che
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Second, while every patient may be unique that does not mean that we cannot develop common processes to cope with our uniqueness. For example, everyone used to have clothes that were made to measure until we found it was much cheaper to mass-produce clothes in multiple different sizes and select the size that fits best using certain particular measurements. The result is something that is certainly not as good as made-to-measure clothes but that still works well and is much more affordable.
For some types of cancer, there are already antibody treatments that work for some people. It turns out that some cancers express certain surface markers, and those markers are often common from person to person. CAR T-cell treatment is, as you said, likely to be used after all those treatments fail.
Since the article didn’t explain it, CAR stands for “chimeric antigen receptor”. In this therapy, T cells are modified to express a receptor that binds to a specific antigen expressed by a p
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We all like to think that no one should have to pay for healthcare
No, we don't.
What most of us do think, at least in the civilized world, is that healthcare should be paid for by everyone via their taxes, thereby then making it available to the same everyone without any further payments of any significance once it is needed.
Of course healthcare must be paid for, or it would not be financed in the first place. The question is just about the method of financing.
The US has got the financing completely wrong.
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By “productive”, you mean manual laborers, I assume — the people whose jobs will soon be done by robots, after which they will be highly unproductive. Most people in higher-skilled jobs are less physically active than they should be.
Re: CAR-T is just too expensive (Score:2)
Cancer treatments are too lucrative for BigPharma (Score:1)
So don't expect an cures.
Everything is about patenting medical progress.
A Dutch university found that baking powder was a cure for certain types of cancer.
The only problem they had was that they could not find a way to patent their discovery as backing powder cannot be patented.
So they didn't continue with the study.
What point is there is making a great discovery in medicine if you can't own the discovery?
Re: Cancer treatments are too lucrative for BigPha (Score:2)
I'm going to have to ask for references on this, because I know Dutch hospitals and they would never ignore a cure for cancer even if it wasn't profitable. They could just create it in their own pharmacies and they are free to use it for "research purposes".
This sounds like an urban legend to me.
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Citation, but without the conspiracy theories:
https://www.ncbi.nlm.nih.gov/p... [nih.gov]
Briefly, baking soda in combination with other treatments could improve outcomes. It's not going to cure all cancers.
Cures as lucrative as treatments (Score:3)
So don't expect an cures.
I often hear waffle like this and it stems from a misunderstanding of what cancer is. Cancer is you, cancer is your own evil twin, the problem is that a 9mm pistol is a cure for cancer, unfortunately it kills you too. The same applies to the many treatments they come up with, a lot of them work well in a petri dish but in a real person the treatment can't tell the difference between cancer and you. This is also why you lose your hair, have bad skin, stomach lining from cancer treatments, they target growing
Re: Cancer treatments are too lucrative for BigPha (Score:2)
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I never heard of an armored Model T
In WWI the British used Rolls Royce's as chassis for armoured cars (in the desert, not the european front)
The fifth pillar. Of four? (Score:4, Funny)
No surprise that Sloshdat Oditurs can't count.
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There are three kinds of people in the world: those who can count, and those who can't.
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Well, it's technically not wrong. You can give a list of examples after the word "like", and there is no grammatical requirement or even normal expectation that such lists of examples need to be complete. Of course, when the list is only 4 items long and they give three, it is a bit jarring (why not just list one more item and complete the list?), but it doesn't necessarily mean that they thought that 3=4. In this case, if they didn't want to give the complete list, they should have limited it to 1 examp
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We know where messing with T Cells gets us. (Score:2)
Costs could come down on t his (Score:2)