CRISPR cancer trial success paves the way for personalized treatments

https://www.nature.com/articles/d41586-022-03676-7

by dsign • 4 years ago

780 273 4 years ago

dsign• 4 years ago

Despite what the article says, this can't be more complicated than producing 5 nm process chips. It's just less funded.

dekhn• 4 years ago

Making safe and effective medicines is a lot harder than modern chip production because the subject is humans and we have to do medicine ethically.

The pharmaceutical industry predates chiptech by quite some time, represents a fairly large market, the companies are quite technological, but the underlying problems are very different from making chips. And if trials like this succeed, that area of biotech will see billions in funding.

It's not funded as much as chips but it's also a smaller overall market.

ethbr04• 4 years ago

this can't be more complicated than producing 5 nm process chips

Chips don't randomly decide to unmake themselves: there's no active, living system you're interacting with.

The other thing that makes biology so confounding is its diversity. E.g. something that works without side effect for 100,000 people will kill 1 of them, because they were in some way different than the others.

bpodgursky• 4 years ago

The regulation and risk-aversion is far more impactful than the funding.

It's not entirely unwarranted regulation, but fundamentally Intel can mess up 20 batches of 5nm chips before getting it right, and nobody cares. If a CRISPR trial kills someone, it's a BIG DEAL, and could potentially set the field back by years.

loeg• 4 years ago

You think the cancer / biotech industry is less funded than 5 nm nodes?

Retric• 4 years ago

Cancer finding doesn’t all go to any one approach, so you can draw the lines fairly arbitrarily around each problem.

brutus1213• 4 years ago

Yes. I think any of the major sport franchise is more well funded than most forms of cancer research.

rjdagost• 4 years ago

I have worked in both semiconductor manufacturing and drug discovery industries. Reliably and profitably producing 5 nm chips is an extreme engineering challenge, but- it is an engineering challenge. Drug discovery is a question of science and requires a fundamentally different mindset that semiconductor manufacturing. Human biology is much more complicated than manufacturing chips (and that is extremely complicated); drug discovery is about "unknown unknowns". Discovering a drug that has the intended effects without causing terrible adverse effects is something that some of the best-funded companies on the planet struggle with.

guelo• 4 years ago

Some of the best-funded companies on the planet also struggle to produce 5nm chips.

thomastjeffery• 4 years ago

But this isn't about drugs. This is about editing genes to manufacture T cells. That's a lot more like engineering than drug trials.

lost_tourist3• 4 years ago

Drugs ultimately have to be converted from the lab to mass production. How is it any different, they all require research, iteration, and ultimately (hopefully) engineered mass production?

borissk2• 4 years ago

High performance computers bring far higher economic benefits than curing some types of cancer, so naturally they are better funded.

breck• 4 years ago

Biology is OOM more complicated than electronics, IMHO. (Background in software then joined UH Cancer Center in 2018)

bragr• 4 years ago

Is the end state of this to eventually modify people's bone marrow to produce modified T cells, or do they envision treating people with infusions of modified T cells? On one hand, permanently modifying people's immune systems seams fraught with challenges. On the other, a steady supply of cancer killing T cells sounds like a strong protection against recurrence.

ethbr04• 4 years ago

It sounds like the "treating people with infusions of modified T cells" approach.

nine_k2• 4 years ago

People's immune system gets irreversibly changed with every new infection it fends off.

pishpash2• 4 years ago

The end state might be a little machine inside that does all of it without specific treatment, i.e. an enhanced immune system that knows what "cancer" is.

airstrike2• 4 years ago

The end end state is a bigger machine that replaces everything except the brain, i.e. an enhanced body that knows that "metabolism" is

candiodari5• 4 years ago

CAR T-cells are cytotoxic T-cells modified so they do not cooperate with the rest of your immune system (they do reproduce inside your body, they just don't care what your "normal" immune system thinks on the matter). They do not listen to instructions from your immune system. They are modified from your own immune system so they don't get attacked, your immune system can't tell the difference between its own cells and CAR T-cells.

They are then further modified to go looking for specific targets (they go through your body, randomly, and check for specific molecules on cell membranes), and become "cytotoxic" towards them (they fire exploding acidic "bubbles" that digest a target cell).

Needless to say, this is a very dangerous treatment (uncontrolled killer T-cells roaming around inside your body multiplying ... not hard to imagine what happens if they target normal cells) and small mistakes will kill patients. In addition to directly killing off important cells, they may can also make the immune system overactive (which in fact happened in this study to three of the patients). They have a bad reputation in research for killing off entire batches of test animals when making a small mistake in less time than you'll need to diagnose the problem and, uh, "fix" it (you're supposed to kill test animals when a treatment doesn't work so they don't suffer). This is not allowed, and has to be explained to the authorities when it does happen and has ended research careers.

Normally, or should I say ideally, after multiplying a more-or-less set number of times, they die off and are removed by the body.

So no, this does not modify the bone marrow of the patient. Not at all. It just attacks and digests specific cells inside your body and dies off.

rubatuga• 4 years ago

TLDR: It attacks and digests specific cells inside your body and dies off.

dm31911• 4 years ago

This is an ongoing discussion in CAR-T. At the moment we only have 'autologous' CAR-T, which means they are manufactured from our own cells. The big advantage to 'allogeneic' CAR-T is that we don't have to take the time (several weeks) to modify T cells for adminstration, during which patients can die of the disease. 'Off the shelf' would be preferable, but there are lots of problems with trying to use someone else's T cells for the job.

The main issue is that our immune system is very good at removing non-self, so a lot of work would need to go into stopping the immune system doing this.

The article isn't talking about CAR-T though, rather TCR-modified T cells. These are very patient-specific because we have a unique MHC signature (this is why we have to find a 'match' for a transplant recipient). Previously people have taken the T cells from the tumour site, boosted them in the lab, and re-infused with some remarkable and curative results. The outcomes in this trial weren't so great but it is novel to splice in a new TCR.

ethbr04• 4 years ago

This pulls together so many advancements that it would make a 90s oncologist cry.

1) Being able to rapidly sequence the genomes of cancer cells to detect common mutations

2) Computationally simulating those mutations to look for viable T-cell targets

3) Custom building T-cell receptor proteins [0] capable of recognizing those targets

4) Inserting those custom receptor proteins into the patients' own T-cells with CRISPR

Truly, we're living in the days of future medicine...

[0] https://en.m.wikipedia.org/wiki/T-cell_receptor

ramraj074• 4 years ago

It’s good progress but I want to say it’s still not a magical cure - the fundamental idea is flawed - the tumor can and likely will in many patients just mutate the immunogenic epitope.

theptip• 4 years ago

How fast can a tumor mutate to resistance? If we're iterating our therapy faster than this cadence do we win the battle?

dm31911• 4 years ago

I haven't seen evidence of cancers re-mutating mutations. They tend to develop new mutations (as in the clonal evolution hypothesis), and they can completely change their cell surface expression. But I suspect that they are unlikely to mutate an already mutated gene.

I guess for the treatment to be most effective you need to target some of the earlier mutations, rather than a small clone.

From my perspective, and not having read the paper, I thought the technology to predict what TCR would bind a particular peptide on a particular MHC-1 was not there yet.

chasil5• 4 years ago

I might not understand it correctly, but the t4 helper cells don't directly work on antigens/pathogens.

They do stimulate macrophages, and activate b-cells.

This from some cartoons, and the associated book by Detmer, Immune.

ethbr04• 4 years ago

Only tangentially my field, but both cytotoxic and helper T-cells bind on antigens, and indeed this work CRISPR edited anything with a TCR to their (3) preferred, cancer-targeting receptors (for each patient).

The press release has a few more details (in addition to the Nature paper): https://pactpharma.com/news/pact-pharma-reports-data-from-fi...

dm31911• 4 years ago

Your CD4 T cells are basically the directors of your immune system. They license CD8 T cells (T killer cells), B cells and recruit NK and immune cells to sites. The type thought to be most anti-cancer are the Th1, which recruit CD8 T cells and NKs, and are optimised for intracellular pathogens. Cancer can be thought of as an intracellular pathogen because it harbors mutations.

shellfishgene• 4 years ago

Custom building T-cell receptor proteins [0] capable of recognizing those targets

How does this part work? Is this some sort of selection of cells in the lab, or done in silico?

projektfu• 4 years ago

There are processes such as this one. Sequencing specific T-cell DNA gives you the fragments you need to insert into the target genome.

someweirdperson5• 4 years ago

1) Being able to rapidly sequence the genomes of cancer cells to detect common mutations

Only of the cancer cells? How are mutations detected in the 0.4% of the DNA that differs in different human beings? Can't there be non-cancerous changes in the other 99.6% that are present in all cells? Is it just a matter of cost, sequencing both too expensive?

joshuahedlund• 4 years ago

My initial guess would be that they would compare cancerous vs non-cancerous cells within the same human being

doctoring• 4 years ago

The article mentions: "...sequencing DNA from blood samples and tumour biopsies, to look for mutations that are found in the tumour but not in the blood."

This is pretty common for most cancer genotyping tests. (Sometimes they compare tumor with saliva or some other "benign" source, but the principle is the same.)

michaelcampbell• 4 years ago

I have a theory that every 10-15 years or so we look back at the previous 10-15 years in medicine and wonder how we lived through it at all.

uzbit• 4 years ago

Thanks for breaking out all these crucial steps!

Do you know of any journal articles that cover step 3? I'm very interested in how this whole process works and can't seem to find much (paywalled at Nature for this one.)

borissk2• 4 years ago

This is very good news for the wealthy, not so much for the average Joe - it will take a lot of time for this treatment to become cheap enough to be used at scale.

culopatin• 4 years ago

It’s still good news for average joe because at least there is something to look forward to.

danuker2• 4 years ago

Reminds me of this story:

https://spellbinders.org/the-smell-of-baking-bread/

The smell of bread in this story is the knowledge that treatment exists.

vtail• 4 years ago

On the contrary, it’s a very, very good news for an average Joe. Every sufficiently advanced technology starts very expensive. Then capitalism and progress do their job, and it becomes available for masses.

The path to “make it cheaper” is generally easier than the path to “make it possible”.

marricks2• 4 years ago

Couple points:

- MRNA COVID vaccine patents weren’t open sourced or available for the third world but Cuba’s vaccine solutions are

- simple things like dental care aren’t offered in the US

I think you should replace “available for the masses” with available “to the middle classes” which may seem the same to the average HN reader but not the average inhabitant of our planet

cmeacham982• 4 years ago

Every sufficiently advanced technology starts very expensive. Then capitalism and progress do their job, and it becomes available for masses.

http://media2.s-nbcnews.com/j/newscms/2016_33/1676741/epipen...

pishpash2• 4 years ago

That's the easy part.

jojobas6• 4 years ago

When penicillin was just introduced a week's course was about $100,000 in today's money. Today its better derivatives are sometimes given away for free.

chasil5• 4 years ago

That particular problem was solved by a mold-covered cantaloupe from Peoria, Illinois.

"After a worldwide search in 1943, a mouldy cantaloupe in a Peoria, Illinois market was found to contain the best strain of mould for production using the corn steep liquor process."

https://en.wikipedia.org/wiki/Penecillin

candiddevmike• 4 years ago

How does this compare to mRNA treatments for cancer?

_joel2• 4 years ago

They're both in vary nascent stages in terms of having a comparable dataset in my layman's understanding. Both look extremely promising, some may be better suited to different classes so that's what larger studies will hopefully help detail.

dumbmrblah7• 4 years ago

MD and I work in the field. The technology is called CAR-T, as the article mentioned. It’s been used pretty widely for “liquid” tumors for a while (eg leukemia, lymphoma, and multiple myeloma),but solid tumors are particularly difficult to target using current CAR-T therapy. If this CRISPR tech can be applied widespread to solid tumors that opens up a huge swath of patients that can be treated.

However cost and logistics are a huge factor. CAR-T therapy currently cost about $300,000-$500,000 to treat a patient. Beyond the cost of the immunotherapy you require a huge institutional investment because there are characteristic side effects that occur within the first 30 days of treatment which necessitates patients to be either admitted to the hospital for 30 days or stay in close proximity with daily check-ins (yes the cancer is getting treated BUT now your immune system is hyperactive which can be very dangerous in the short term).

Very few academic hospitals, let alone community hospitals, have this bandwidth which will lead to cancer care being concentrated in a handful of a few very large cancer specific institutions.

aantix• 4 years ago

If money weren’t an issue, which institution/doctor would you send a loved one to if they needed such treatments?

throwaway12245• 4 years ago

You'll want to sign them up for a clinical trial. Only CAR-T cell therapies that are FDA approved are for leukemias. [ and as a commentator points out, for lymphomas, I had always thought lymphomas were a subset of leukemia. mea culpa ]

jojobas6• 4 years ago

Does that $300,000-$500,000 go mainly to super-highly qualified labour, expensive materials or rare machine time? Still more or less on par with a few rounds of chemo.

dumbmrblah7• 4 years ago

Good question and I should have been more clear. The drug itself is $300,000-$500,000. It’s crazy expensive, but it’s not like a hedge fund patenting 100 year old insulin or something, it’s a bespoke medication. I still think they are price gouging however.

The medical care would likely add another $500,000.

https://ashpublications.org/ashclinicalnews/news/3469/CAR-T-...

All in about $1,000,000 per patient.

There were some drama in England about NICE not willing to put the medication on NHS formulary because of the sheer expense. Is it better to treat 1000 diabetics or one cancer patient?

https://www.biopharma-reporter.com/Article/2018/09/21/Novart...

They ultimately approved it.

ThinkBeat• 4 years ago

I sadly know little about all this technology. It is fantastically expensive at the moment from what you say. That keeps it away from the vast majority of cancer patients in the world.

Technology does tend to get cheaper over time, though not always.

Do you think this treatment could reach $30.000 in 2,5,10,15 years? And $300 in another 10,20,50 more years?

solveit• 4 years ago

Technology does tend to get cheaper over time, though not always.

What technology didn't get cheaper?

colinmhayes• 4 years ago

Obviously not op, but it sounds like the issue is that the cure makes you sick in the short term which requires expensive care. If the sickness is inherent to the solution it’s hard to see how this gets cheaper.

nicwilson• 4 years ago

As with many medical drugs, the marginal cost of production of the medication is small, but it is dwarfed by the cost of research, trial conduction and FDA approval and is patented. Additionally for CAR-T there is rather intense post-adminitsation care required.

For the pharma research companies to be profitable, they need to recoup the above costs on the limited number of cancer patients there are.

For a widely applicable technology like CAR-T, if you can figure out how to distribute the costs over multiple types of cancers, you could have a much larger pool of patients to distribute the cost over, such that the marginal cost of production is a more meaningful component of the cost to patient/insurer.

heavyset_go• 4 years ago

I've watched the prices of patented drugs quadruple in less than 5 years, to the point where a 30 day prescription can cost thousands of dollars despite the same medication costing $40 in countries like the UK. Drug companies have absolutely no reason to drive down prices of the patented treatments they have a literal monopoly on.

rmak• 4 years ago

Cancer won't be a problem by 2027, at least for the people who don't already have cancer. By 2030 there will be drugs that can even cure stage 4 cancer with next to nothing side effects. (AI and some form of quantum computing will help find these drugs)

chefkoch• 4 years ago

Another therapy mentioned often in the comments here CAR-T is at the moment around 300k from the pharmaceutical companies.

A study in germany predicts a cost of around 30k if universities or other bigger health care providers create the CAR-T cells in their own labs.

120photo3• 4 years ago

Do you know if CAR-T or CRISPR technology goes into the brain?

dumbmrblah7• 4 years ago

There are clinical trials on Glioblastoma CAR-T treatment but it faces the same problems as any other solid tumor - namely the solid tumor microenvironment is not amenable to the current generation of CAR-T treatments

In addition one of the dreaded side effects of CAR-T is neurotoxicity. CAR-T can cross the blood-brain barrier and leads to inflammation in the brain. You can treat it pretty quick with steroids but this side effect along with several other pro-inflammatory ones is the reason for the 30 day hospitalization sp treatment.

erisian3• 4 years ago

Not CAR-T or CRISPR AFAIK, but there's been some recent breakthroughs with getting treatments past the blood brain barrier, and promising glioblastoma treatments are in the pipeline as well. This is just what I've seen on the internet news, you'd find more than I know about it with some internet searches.

I hope you aren't affected by GBM. If you are, or someone you know is, my only advice is to live life to the fullest while you can and don't let yourself fall into denial of the prognosis.

ramraj074• 4 years ago

Are you sure THIS treatment above is only 500k? It’s too bespoke and no way I can imagine it costing less than a few million per patient.

dumbmrblah7• 4 years ago

I responded to another post similar down but you are correct. The drug is $500k, the surrounding medical care / hospitalizations etc pushes the total cost to over $1,000,000

dm31911• 4 years ago

OP is talking about CAR-T therapy which is in routine clinical practice. In the UK costs have gone from £600k to around £250K That includes the surrounding medical, nursing and follow up care. In the US costs are likely to be more than that.

The article is talking about a very bespoke process where they take a patient's cancer, sequence the whole thing, select mutations they think will be presented on MHC-1, predict the antigens visible, and 'somehow' (I need to read the article more carefully to figure out how they did this) select a TCR sequence which will bind to that. Then they use CRISPR to graft that onto the TCR gene of a T cell from the patient (3 types by the looks of it), and re-infuse the targeted cells.

So yes, that would cost several million.

fnordpiglet• 4 years ago

This sounds like something that works out with time and scale. Thanks for the insight.

bobmaxup• 4 years ago

which will lead to cancer care being concentrated in a handful of a few very large cancer specific institutions

Wouldn't that be a good thing? Aren't specialized hospitals better at treating things that they specialize in?

ugh123• 4 years ago

From what OP said, I doubt they'd be able to keep up with the additional load of patient care (admittance especially) so there could be long wait times.

At some point, capabilities like this mature on the science end but are slowed down on technology (scaled manufacturing). That would take significant investment by a big pharma or a new venture-backed investment to go after things like this. Fingers cross this happens within my lifetime.

From the article: >“This is a tremendously complicated manufacturing process,” says Joseph Fraietta, who designs T-cell cancer therapies at the University of Pennsylvania in Philadelphia. In some cases, the entire procedure took more than a year.

dumbmrblah7• 4 years ago

Good for people with money, resources to know where to get the best treatment and live close by; bad for everyone else.

Disclaimer: I work at a giant cancer institution.

daguava• 4 years ago

Is that the real COST or the markup "cost"

yosame2• 4 years ago

Probably both, they've got to make back the cost of developing and testing the therapy, but there's probably a profit markup on top of that.

xeromal• 4 years ago

Don't forget R&D costs

inglor_cz• 4 years ago

The madness of the US healthcare aside, CAR-T is really a somewhat complicated therapy. There are no economies of scale there, unlike in pills. Each patient requires a lot of painstaking work that can only be done on specialized machines by highly qualified people, plus the safety requirements are really high.

Activating the immune system is risky. It is strong and it can crush cancer in mere weeks, but it is also very dangerous to friend and foe alike. Basically, you gather a lot of absolutely ruthless and stupid troops and tell them "here is ze Flammenwerfer, burn the enemy to crisp, but don't destroy anything else".

Easier said than done.

derefr• 4 years ago

yes the cancer is getting treated BUT now your immune system is hyperactive which can be very dangerous in the short term

Can immune-suppressive drugs be used during treatment?

lll-o-lll• 4 years ago

Ahhh, personalised treatment for the mega rich. Soon our billionaire gods will be able to live far beyond a normal lifespan. I wonder how this will impact society?

noduerme• 4 years ago

If it wrecks the rest of social media the way it's on its way to destroying Twitter, could be a long term good for everyone.

quickthrower22• 4 years ago

Rich get a few years head start while effectively financing the making it cheaper part. Not “fair” but at the same time there is trickle down.

dm31911• 4 years ago

This isn't CAR-T, which is a chimeric antigen receptor (antibody) grafted onto a T cell. This is a T cell with an edited TCR receptor. This is quite different and comes under the 'adoptive TIL' category of treatments. It allows targeting of antigens not displayed on the cell surface. Every cell has to process their protein through a proteasome and present those peptides on the cell surface, which is where the advantage of this type of treatment comes in. In CAR-T we target a surface protein, and there's nothing to stop the cancer removing that protein from the cell surface.

tauwauwau• 4 years ago

How do hospitals spend $10000 to $16000 a day?

a99c43f2d565504• 4 years ago

To pay the people who make these things happen I suppose.

polar• 4 years ago

What is MD?

texasbigdata2• 4 years ago

Medical Doctor in the United States. Undergraduate (4 years) + Med School (3 years) + Residence (1 to 3 years), roughly.

marstall• 4 years ago

For comparison on the cost question:

I received conventional, pre-CAR-T treatment for ALL Leukemia about 9 years ago. That consisted of chemo, total body irradiation and a successful bone marrow transplant. Cost was $300,000.

queuebert2• 4 years ago

All of you AI people reading this should work on predicting side effects and outcomes from these therapies. That would help decrease the cost tremendously.

UltraViolence• 4 years ago

And the first sequencing of the human genome took 10 years and cost hundreds of millions of dollars. Today you can do it for $100 in a couple of hours.

The same will happen with CAR-T and CRISPR.

sniperjoe3602• 4 years ago

"Five patients had stable disease, and the other 11 had disease progression as best response on therapy"

great science, but disappointing clinical results

awillen• 4 years ago

Although the efficacy of the treatment was low, the researchers used relatively small doses of T cells to establish the safety of the approach, says Ribas. “We just need to hit it stronger the next time,” he says.

_joel2• 4 years ago

They did a low dose as this is new technology, the next round will have a higher count, so hopefully we'll see greater efficacy.

joshxyz• 4 years ago

shit man i pray to fucking god for better resutls

TaupeRanger• 4 years ago

They weren't trying to get results, only giving a low dose to verify acceptable side effects. Wait for the larger doses to render judgement on clinical results of the treatment modality itself.

sniperjoe3602• 4 years ago

I completely agree with you. If there was even one response I would be much more optimistic. Since there is no clinical signal this is at best a proof of concept and safety.

chasb• 4 years ago

My 27 year old sister got CAR-T for leukemia earlier this year after a failed stem cell transplant. She's in remission. It's incredible, literally curing cancer.

znpy• 4 years ago

I’m happy for you, best of luck to your sister.

gleenn• 4 years ago

If you don't mind me asking, how was her pain for the 30-days after period? Another poster said they were extremely lucky to only have suffered a few fevers but some people were in a coma.

teaearlgraycold• 4 years ago

Had no idea we were at this point. But I’m so glad! Hope your sister lives to be 100.

dis-sys• 4 years ago

Incredible, hope your sister's remission to be a complete & permanent one.

Literally curing cancer, just incredible.

jmacd• 4 years ago

My friend's 68 year old mother also had it (after being quite sure she was facing a fairly rapid death after other treatments failed).

She's pretty much back to normal. I might say better than before as she now takes her overall health much more seriously.

Amazing.

29_29• 4 years ago

My mom has a very serious type of Breast Cancer, Triple Negative, so this news is very encouraging. She's undergoing immunotherapy - but this looks even more promising. Thanks for posting.

daniloalmeida• 4 years ago

yay. I read the headline in order to be elated. Now I'll read the article to get carefully optimistic and then I'll visit the HN comment section to come crashing down.

lost_tourist3• 4 years ago

Nah just a reality check. This will only work for very rich people. However as they learn more and costs come down it can trickle down to us plebes :)

thret• 4 years ago

I read an article (or watched an interview) a few years ago, where they were saying that because cancer is unique to the individual, to truly cure cancer you would have to target each cancer individually. Hence CRISPR. But they also warned that this kind of control could also be used to target individuals or groups of individuals. The example they gave of what could theoretically be possible was 'making women of a certain racial group hyper sensitive to sunlight'.

Was this hyperbole? I can't find any references to it today.

piyushpr134• 4 years ago

As per the article, calling this a "success" is a little over the top. Out of 16 patients, it stopped progression of tumour in 5 had stopped but it doesn't say it decreased. Moreover for 2, it had adverse reactions when admittedly the dosage was low. I won't call that a success. IT is a good start and promising result. "Success" would mean at least 50% patients REDUCED the tumour. So let us not hold our breath yet

timbit422• 4 years ago

While removing the cancer cells would be preferable, killing them all so they no longer replicate means the patient will not die from that cancer.

dm31911• 4 years ago

I'm a haematologist who is involved with patients who have CAR-T (I don't do it myself, but do other types of transplant and I look after the patients before and after) and my research area is in the way T cells target cancer.

This study isn't CAR-T. It is more similar to adoptive TIL therapy because it is using the T cell receptor (TCR) to target the cancer's mutations. This has a huge advantage over CAR-T.

At the moment we use CAR-T to target, mostly, B cell cancers. These cancers have CD19 and CD20 on their cell surface, as do most B cells. We can safely target these cells because it turns out your B cells aren't critical for life. Think of it like an amputation. Your B cells went rogue, you wipe them out.

The problem is this doesn't translate to other cancers, which don't have an obvious cell protein you can target specific to a group of cells you can do without.

All cancer cells have mutations, and all cells in the human body have to display a sample of its proteins on its cell surface. This way our immune system regularly identifies cancer and removes it. Cancers that get established have somehow leveraged local immunosuppression to hold off the immune system, and so the immune system and cancer become a stalemate, or worse the cancer takes off and kills the person.

If we can target the mutations of the cancer, then we can get at the heart of the cancer itself.

You might ask why the cancer just doesn't display it's antigens on the surface. If a cell does this it gets removed by NK cells (natural killers) - our body's fail safe.

What I find interesting is that I didn't think we were close to predicting what TCRs can bind to to a peptide on MHC on the cell surface. I'm going to need to look at the article to findout how they did this. I suspect they used a library of known TCR-antigen interactions.

readittwice• 4 years ago

Since there are people here that seem to know a bit about this stuff, I will take the chance to ask some naive questions ;)

Do I have this right that CAR T-cells have this engineered B-cell/antibody like receptor that recognizes antigens only on the cell membrane. While the regular T-cell receptor can look into cells as well? And that's why the T-cell receptor is potentially better at recognizing solid cancers?

So cancers usually create this immunosuppresive environment, wouldn't this stop this engineered T-cells as well?

dm31911• 4 years ago

Yes, CAR-Ts are really a B cell receptor (otherwise known as an antibody) grafted onto a T cell. Antibody directly binds things like proteins, and usually targeted to things found on cell membranes.

Also on the cell membrane is MHC-1, which shows a short (9-11 amino acid) fragment of protein produced from inside the cell. Our T cells are trained in our T cell kindergarten (the thymus) to not identify our usual self proteins, but detects anything different. They have already been demonstrated to identify single amino acid changes from normal.

Yes, the micro-environment means the immune cells reach a dynamic equibrium. This is because when a cancer presents to healthcare, it is already a chronic process. The T cells are termed 'exhausted', but it's debatable whether this is a good term for it, because they are still active.

A lot of cancer treatment 'shakes up' the microenvironment. This can be enough to tip into a cure. When you make CAR-Ts and adoptive TILS you either pick healthy T cells not involved in the cancer or buff them up in the lab, both in numbers and health.

The hope is that a refreshed army of T cells will push that dynamic equilibrium towards a cure.

roschdal• 4 years ago

Cure for cancer, nice.

ck2• 4 years ago

Random but CRISPR babies are going to sweep the Olympics in 2040

China and Russia have to be fiddling with it at this point and it will either be completely undetectable or un-bannable in competition by then.

timbit422• 4 years ago

It won't be undetectable. If the changes are something no one else on earth has, it will show up. If the changes are something other people have, it will still show up when comparing with their parent's DNA.

midoridensha5• 4 years ago

What if the "changes" are simply optimizing someone's genetics? i.e., eliminating /fixing any genes that are bad mutations, so you get the best possible combination of genes from the parents?

Or, suppose someone really does have a beneficial mutation that naturally occurred, and isn't the product of genetic engineering. Are you going to disqualify them because neither of their parents had the mutation?

yieldcrv• 4 years ago

I love that this form of reproducible science converges with the goals and beliefs of holistic practitioners which relies on non-reproducible methods

Maybe the latter will go away once we have holistic/personalized solutions via CRISPR

6stringmerc• 4 years ago

Too bad the Baby Boomers spent all their money and won’t have enough to enjoy these new innovations. Blood letting in the poor house for you buster!

khnov• 4 years ago

My father has cancer on stage 4, he probably will die soon, can anyone help me try this on his case ?

CRISPR cancer trial success paves the way for personalized treatments

Related Stories