New T-cell Has Potential for Universal’ Cancer Therapy

Researchers at Cardiff University have discovered a new type of killer T-cell that offers hope of a “one-size-fits-all” cancer therapy.

T-cells with the new TCR were shown, in the lab, to kill lung, skin, blood, colon, breast, bone, prostate, ovarian, kidney and cervical cancer cells, while ignoring healthy cells. The researchers injected T-cells able to recognise MR1 into mice bearing human cancer and with a human immune system. This showed encouraging cancer-clearing results which the researchers said was comparable to the now NHS-approved CAR-T therapy in a similar animal model.

The Cardiff group were further able to show that T-cells of melanoma patients modified to express this new TCR could destroy not only the patient’s own cancer cells, but also other patients’ cancer cells in the laboratory, regardless of the patient’s HLA type.

CAR-T and T-Cells

T-cell therapies for cancer – where immune cells are removed, modified and returned to the patient’s blood to seek and destroy cancer cells – are the current hottest thing in cancer treatments. The most widely-used therapy, known as CAR-T, is personalized to each patient but targets only a few types of cancers and has not been successful for solid tumors, which make up the vast majority of cancers.

T-cell therapies have been making slow progress because each type of cancer needs specific modifications that require their own clinical trials.

Cardiff researchers have now discovered T-cells equipped with a new type of T-cell receptor (TCR) which recognises and kills most human cancer types, while ignoring healthy cells.

Nature Immunology – Genome-wide CRISPR–Cas9 screening reveals ubiquitous Tcell cancer targeting via the monomorphic MHC class I-related protein MR1.

How does this new TCR work?

Conventional T-cells scan the surface of other cells to find anomalies and eliminate cancerous cells – which express abnormal proteins – but ignore cells that contain only “normal” proteins.

The scanning system recognizes small parts of cellular proteins that are bound to cell-surface molecules called human leukocyte antigen (HLA), allowing killer T-cells to see what’s occurring inside cells by scanning their surface.

HLA varies widely between individuals, which has previously prevented scientists from creating a single T-cell-based treatment that targets most cancers in all people.

But the Cardiff study, published today in Nature Immunology, describes a unique TCR that can recognise many types of cancer via a single HLA-like molecule called MR1.

Abstract

Human leukocyte antigen (HLA)-independent, T cell–mediated targeting of cancer cells would allow immune destruction of malignancies in all individuals. Here, we use genome-wide CRISPR–Cas9 screening to establish that a T cell receptor (TCR) recognized and killed most human cancer types via the monomorphic MHC class I-related protein, MR1, while remaining inert to noncancerous cells. Unlike mucosal-associated invariant T cells, recognition of target cells by the TCR was independent of bacterial loading. Furthermore, concentration-dependent addition of vitamin B-related metabolite ligands of MR1 reduced TCR recognition of cancer cells, suggesting that recognition occurred via sensing of the cancer metabolome. An MR1-restricted T cell clone mediated in vivo regression of leukemia and conferred enhanced survival of NSG mice. TCR transfer to T cells of patients enabled killing of autologous and nonautologous melanoma. These findings offer opportunities for HLA-independent, pan-cancer, pan-population immunotherapies.

SOURCES- University of Cardiff, Nature Immunology
Written By Brian Wang, Nextbigfuture.com

41 thoughts on “New T-cell Has Potential for Universal’ Cancer Therapy”

  1. Yea, yea, regulation is wonderful, that is why you are legally allowed to drink battery acid but ingesting a experimental drug that could actually treat your disease is strictly forbidden of course. I mean, where would we be when patients and doctors actually decide what drugs they try or not.

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  2. Yea, yea, it would be utopia if not for regulation.
    Most doctors would not give this to a terminal patent without much more research, ever hear about “Do no harm”?

    Colorado was first in 2014, 30 states had already enacted a “right to try” law when California adopted one in 2016.

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  3. Accidents, suicide, and murder, especially accidents, take the form of physical trauma. And treatment of physical trauma has gotten much, much better over the years.
    There is no basis to saying that this is not being actively tackled.
    Indeed, we’ve seen several articles here in NBF about improved bleeding suppression and stuff like that. Often sponsored by the military.

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  4. Not true. Many young people suffer from psoriasis, rheumatoid arthritis, type 1 diabetes, etc. And many young people get cancer.

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  5. Strokes would be reduced by any treatment for arteriosclerosis (reduces blood pressure), atherosclerosis (we saw an article on this one recently, prevents the plaques that break free and cause some types of strokes), weight loss, or diabetes.

    I can’t remember if I’ve seen them here but there is work on the sort of dramatic treatments for diabetes that would be called a “cure”, and even if that takes a long time, diabetes can be managed with a low carb diet and exercise. Any treatment that causes significant weight loss would also help, and we have seen articles on here about research into promoting brown fat and so on.

    Finally, improvements in senolytic drugs would probably reduce kidney disease, and of course it would be solved entirely if we actually got good at growing replacements in pigs using crispr-immuno-engineered human stem cells.

    So pretty much everything aside from accidents, suicide, and murder are being actively tackled right now.

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  6. Yes, current treatments is pretty much like calling down an air strike on your own position. It can work because you are dug in and the enemy is in the open. But unless you are in an real bunker you will take heavy causality yourself

    Lost an big toe myself because of cancer, it came back but then they found it was preliminary cancer.
    Its an condition who is far more dangerous than an benign tumor, but is unlikely to develop into real cancer.
    Preliminary cancer was discovered during the mass screenings for breast cancer. They got lots of more tumors than people who would get breast cancer.

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  7. Or anybody past their reproductive age as anything past that is not passed down to your children.
    However its one effect special for humans who make old people useful.
    They can teach kids and do various task at the camp like making food or tools even if not able to hunt.
    But this is an far slower and more limited process.

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  8. Actually, the Republicans passed the “right to try” law a couple years back. I am not well versed on it but it may in fact allow someone to try this treatment even though it is not FDA approved yet.

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  9. My take on cancer is that if our immunity system is too aggressive it damages our organs and we die of organ failure like heart attack or renal failure. And if it isn’t aggressive enough we die of cancer.

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  10. The fact that we are one of the few mammals that live into our seventies and beyond indicates that we have an immunity system that has evolve to protect us against cancer. Being hot blood means we generate a lot of DNA damaging free radicals which isn’t good for our long term survival. We live long because our children need a lot of long term care than some times span generations.

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  11. The problem is not to find willing patients – hundreds of patients die horrible cancer deaths every day – but the problem is regulation.

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  12. Personally, I would even skip part of the animal testing phase. If one has few
    weeks left, he has not much to lose from a risky therapy.

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  13. So, from what I’ve seen lately, there now exist:
     
    – a possible experimental cure for heart disease/arteriosclerosis (23.5% of U.S. deaths)
    – a possible experimental cure for cancer (21.3%)
    – experimental self driving cars to prevent traffic accidents (6%)
    – cut backs in smoking to drastically reduce lower respiratory disease (5.7%)
    – possible experimental cures for Alzheimer’s (4.3%)
    – possible experimental universal flu vaccine (2%)
     
    If all that pans out then we can all look forward to:
     
    – strokes and cerebrovascular disorders (5.2%) — some progress studying zebra fish
    – diabetes and kidney disease (4.8%) — possibly reduced 30% by canagliflozin
    – suicide (1.6%)
    – murder (about .006% on average)
    – or something really weird, trampled by an elephant, being hit by a falling piano, etc.

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  14. Exciting news.

    My sister had breast cancer, cured it, then ot leukemia. I donated my bone marrow to her (luckily, both of her siblings were 100% compatible with her). But some new breast cancer spots appeared less than one year after the bone marrow transplant.

    It’s her 3rd year of struggle against cancer.

    And my sister in law just removed her breast…

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  15. Likely the former. Cancers aren’t common enough among the under 40s for it to have been advantageous to anyone but medieval kings.

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  16. The technical term is “survived”, and for good reason: You’re remarkably lucky if the experience doesn’t leave you with permanent medical consequences. Chemotherapy works by almost poisoning you to death, in order to successfully poison to death the cancer. Being repeatedly almost poisoned to death over a course of months leaves its mark on you.

    One of the exciting things about the procedure in the OP is that it *isn’t* based on that concept, and would likely kill the cancer without leaving you a wreck.

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  17. They isolated equivalent T-cell lines from two different people. So at least some people do have it, and it might actually be present in all of us. The research noted that it in mice it didn’t manage to eliminate their cancer entirely, but basically kept it in remission. This might be significant.

    We know that young people with healthy immune systems get cancer at much lower rates than elderly people with poor immune systems. We know that many cancers are kept in some early stage where they never spread much and are benign.

    So, perhaps this type of cell is actually the primary cancer immunosurveillance mechanism we already use. Then the real question isn’t “Why don’t we already use this?” (because we already do), but rather, “Why does it sometimes fail, even in the young?”

    Hard to say for sure though. We still don’t really know if this form of T-cell is common in most people or not.

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  18. Yes in essence that is what I am saying. I do know people in big pharma companies and they often have reasonably ethical practices (will donate doses of life saving drugs to people who can’t afford it etc). My point is, for these big companies with existing drugs it makes a lot more sense (and costs a lot less money) to see if their existing portfolio of cancer treatments can be approved to treat another form of cancer (I.e. expand their market) than to invent a new therapy.

    I think the sweet spot of new development for these companies are antibody treatments. That is because it is hard for a competitor to make a generic and much more difficult to get regulatory bodies to approve a ‘bio-similar’ as opposed to a synthetic generic chemical drug. Antibodies like keytruda can be given for a wide variety of conditions and potentially for the rest of the patient’s life.

    I was about to say that treatments like CAR-T cells (which can maybe be more silver bullet type therapies for some people) probably aren’t favourites of big pharma. But then I remembered Novartis (2nd biggest pharma in the world) is the main company supplying CAR-T, so kinda contradicts my argument! Still, I think that companies with existing drugs that can be sold to a patient for several years would, on a commercial level, prefer to be selling those products, compared to a more limited product like CAR-T.

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  19. The idea that “big pharma” is holding back cancer treatments for profit is nonsense. Their CEOs and shareholders or at least members of their families get cancer too, you know. Cancer risk is 35% on average. So yeah, one out of 3 people you know will get it. You think that those “evil big pharma” executives would sacrifice their own families and friends for some potential short term profit? Get a grip!
    Most early research happens at universities. The big problem is clinical trials. Getting something through those is insanely expensive. Finding enough patients that match the requirements is tedious and takes a long time. There are a lot of restrictions and regulations that make this even harder. This is one reason why it takes 10 years or more for a treatment to get from pre- clinical trial stage into the hands of patients. The other problem that this causes is that small outfits can not finance it. They are usually bought by a larger corporation, which then puts the treatment through trials. Having a treatment fail in clinical trials is a costly matter and most treatments fail. So I can promise you that no pharmaceutical company is interested in seeing a product fail in trials. Usually when the news surfaces that some treatment failed, it causes their stock to drop…
    Don’t buy into all that conspiracy crap!

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  20. Agreed! The safer something is, the less afraid people will be to use it, especially for extended periods. I definitely think you’re on point about all of that. I do feel like young doctors will feel more motivated. Risk not only gets your name out there, but it can be ridiculously interesting. The intrigue of what might be possible always seems to have a leg up on what is currently known to be possible.

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  21. I think this is a scaling issue. The CAR-T technology is relatively new, so the logistics of making it happen are more expensive.

    The reason these MR1 binding cells haven’t been discovered is that they (and similar cells like MAIT cells) are very hard to detect until recently and are tiny populations.

    Existing anti-cancer industry can’t realistically stop the invention of these new technologies. They probably aren’t actively lobbying for hampering R&D of new technologies because that will backfire on their own product development pipelines.

    Existing companies are generally more interested in developing better/safer versions of the existing drugs that they can sell to you for the rest of your life. They may be less willing to fund expensive clinical trials that undermine their existing products. These bigger pharma companies may also be able to recruit the best and brightest doctors and scientists to work for them. So, in those ways the can slow down development. However, younger scientists and doctors will be highly motivated to take on riskier/interesting/exciting projects to make a name for themselves. There is also plenty of VC $ out there still.

    Eventually, the older companies will see a new tech winner emerging and will probably buy it and make a combination therapy of chemo + CAR T-cell.

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  22. I feel as though the reason this hasn’t been wide-spread news until more recently is because larger medical industries grown up around treating cancer in other ways, would be harmed. But, with all due respect, screw them.

    Then again, I’m nothing if not WIDLY cynical about the way status quo industry treats disruptive technology that could potentially change the status quo lol >_> I always (and incorrectly) believe entrenched industries are out to stop disruptive and efficient technology.

    Someone who actually knows what they’re talking about (because I don’t): What kind of effect would more efficient and less invasive treatment that stems from the science discussed here, have on the medical industry (specifically the sector involved in treating cancer)?

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  23. Sadly, there are a whole bunch of difficulties and expenses in going from lab to market, of which finding enough willing patients is only one.

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  24. The rarity of such cancers (which can evade existing defenses) during reproductive years means the selection pressure against this type of cancer is quite low.

    Yeah basically this. I think there are a range of evolutionary selection pressures here. Likely there are large selection pressures on other anti-cancer mechanisms like DNA repair enzymes (or just not being born with germline mutations).

    The other thing is that we do have some anti-cancer immune cells. Natural Killer (NK) cells and Cytotoxic CD8+ T cells will kill both viral/bacteria infected cells and cancerous cells. Using the main molecules of the HLA/MHC antigen presentation system has worked very well for both viral/bacterial and cancer, so possibly production of those cells is evolutionary emphasised. In solid tumours the NK/CD8+ cells get suppressed by the tumour microenvironment. The MR1 targetting cells might likewise be present but get suppressed before they can execute their killing functions.

    The other thing in all this, is that this is new research. The authors think the MR1 is expressed widely in cancer cells. It may be that in actual patients, many cancers might downregulate MR1 but we just haven’t tested that hypothesis.

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  25. The human body does do this, which is why the unknowable number of mutated cells that naturally occur in the human body are normally eradicated. One of the mysteries of cancer comes back to the fact our immune system should eliminate mutated cells, but for some reason, whether it be age or disease, the immune system of some people isn’t as effective.

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  26. Having lost a sister, and a cousin who was like a sister, to cancer, and having had cancer myself twice, this is thrilling news.

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  27. Possibly implementing it requires multiple mutations, any one of which by itself is either deleterious or at a minimum does nothing that would cause it to be selected for.

    Evolution is a hill climbing algorithm, it has a very hard time taking paths where some of the individual steps take you down, not up.

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  28. Wondering why this strategy hasn’t already been selected for in our genetics. If this is a receptor common to many cancers, but to no productive tissues, wouldn’t our immune system already use this?

    I see two possibilities:

    1. The rarity of such cancers (which can evade existing defenses) during reproductive years means the selection pressure against this type of cancer is quite low.
    2. Use of the receptor to terminate cells is selected against because it has some deleterious effect on the organism / reproduction.

    Am I missing any other possibilities here?

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  29. It should be very easy to bridge the gap between lab and human tests as there would be countless people with cancer willing to give this a crack

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