What we are doing today with CAR-T cell therapy against cancer seems like SciFi | Hacker News Reader

What we are doing today with CAR-T cell therapy against cancer seems like SciFi

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I just want to emphasize that, currently, CAR-T therapies are not particularly effective for solid tumors, which make up the majority of cancer diagnoses. They're currently only good for leukemias and lymphomas. They're also not the first line of treatment, because they have to be genetically engineered from your own cells, and then reinjected into you.

There's been some progress in CAR-NK therapies, which would be "off the shelf" in that they don't need to be engineered from your own cells. Also some very preliminary work with allogeneic CAR-T therapies that wouldn't have to be made special for each person.

Is there any reason why the price for personalised CAR-T therapies couldn't come down dramatically? Just like the price of genome sequencing has come down?

I'm curious as well. The article mentions $300,000 for a treatment. Can anybody give a rough breakdown of where that money goes? How much is labour / ingredients / profit?

I am watching someone go through this treatment at the moment. I was trying to describe the process to a friend and after giving my understand had to follow up with "it seems fantastical, or like magic, in a way that is hard to wrap my head around."

The monitoring time post treatment seems like it might be a bigger bottleneck than the production time but it could be that as the side effects and likelihoods are better understood then that level attention might be reduced. I was told that currently there are only two production facilities, one on each side of the country.

During the blood collection recently one of the nurses talked about the possibility to work on sickle cell anemia and how they were hoping to start treating people. https://www.npr.org/sections/health-shots/2023/10/31/1208041...

I work in the OT/automation space for pharma. Cell and gene therapy is crazy amazing.

One thing I didn’t really see mentioned here is length of treatment. They have to collect patients sample at hospital or other facility, transport to production facility, grow sample, inject sample with vector, grow some more and then reintroduce. The real sci-fi moment will be when they get to the point they can treat in a day.

I think most are 3+ weeks sample to treatment right now. Still amazing though.

There are a number of companies working on 'in vivo' deliveries for CARs. Oftentimes using the same tools as proven out by the Moderna vaccine.

Yes, but that way you lose control over the dose, and to an extent over CAR-T characteristics. CAR-T therapy is usually used in patients who already had multiple rounds of chemo and their immune cells are generally not in a great shape. Even with 'traditional' CARs you occasionally get manufacturing failures since the cells are too exhausted to expand in vitro or have already lost their effector functions.

The 'vein-to-vein' time (apheresis to infusion) is being shortened all the time, and you can already manufacture CAR-T cells in 24-48hrs, but it still takes about a week to clear quality assurance and release the product (microbiology, integrated copy number, integration site testing, autonomous growth potential etc). The reason being mostly that you don't want to accidentally replace patient's B cell cancer with a T cell cancer of your own making.

Hah, you don’t have to tell me about validation and quality. Yes, they usually account for a significant time of anything in the pharma world.

> The real sci-fi moment will be when they get to the point they can treat in a day.

How do you imagine that would work?

Some closed-pipeline machine that lives in the hospital and automates sample → modified sample culture cycle?

Or something stranger, e.g. some kind of injectable (maybe prokaryotic?) cells that actively swim around looking for L-lymphocytes to vectorize through bacterial horizontal gene transfer — such that the whole process happens in vivo?

> Some closed-pipeline machine that lives in the hospital and automates sample → modified sample culture cycle?

That's already a thing, for example Lonza's Cocoon platform or Miltenyi's Prodigy (both are often used for on-site manufacturing).

would you mind sharing what you think are the largest bottlenecks to (1) 24-hr turnaround and (2) CAR-T therapy for < $10K?

I think that's near impossible to achieve with an autologous product. To meet those two goals I think you'd need to have an allogenic product manufactured and QCd in advance in a large batch, which you could thaw and infuse on demand. The problem with that approach is histocompatibility (HLA) matching, but several companies are working on that.

thanks for sharing. this is such an impactful space. hopefully someone one day can lower the cost to $10K or ideally $1K.

Considering leukemia treatment today is 2 years for girls and 3 years foe boys, 3weeks is several magnitudes worth of improvement.

The treatment itself is a one-day procedure (although the patients will be generally kept under observation for CRS for a few days and then regularly monitored for response), the 3 weeks is the time needed for manufacturing/QC. In that time patients receive bridging chemotherapy until the CAR-T product is ready and unfortunately some do not make it.

You're quoting the length of Course V Maintenance in the CALGB 10403 study (or similar pediatric COG studies on which that was based), which is misleading in that it is (a) applicable only to ALL (b) patients under 40 y (c) only the final of five courses of treatment.

That being said, you're directionally correct and certainly, shorter duration immunotherapies represent a sea change.

Currently a PM at the NMDP OneForum event talking to all the people driving this research. It is incredible being in a room of researchers, doctors, and providers of these types of therapy. I'll say a lot of the ordering systems could use the graceful touch of some of the HNers here, but I am in awe of what this group is capable of. Mad respect to all the people involved.

I have a child who was treated for ALL. As I researching the history of it I felt I was living in the time of Science Fiction. A generation or two before there was no treatment and with my child they were doing very specific genetic tests to tune chemo treatment levels to his specific version of ALL. We spent a couple of months in the paediatric oncology ward, 70% of his cohort (mixed cancers) in the ward did not survive his 3 year treatment cycle. My sister-in-law had stage 4 melanoma with 6 months or less prognosis. She was entered into an immunotherapy trial. 8 years later she is great. However, she was the only one out of 6 who survived in her trial. I don’t know all the details but all others withdrew - it was not a fun ride.

It is truly an amazing time.

Is this similar to Personalized OncoGenomics aka POG? I speed read it but it's near 1am here so I'm a big foggy brained.

https://www.cbc.ca/natureofthings/features/everything-you-ne...

If you zoom out a bit, the doctor looks like Harrison Ford.

That is what I thought as well.

https://assets-prd.ignimgs.com/2023/08/07/harrison-ford-the-...

what a fantastic read! wow.

Hate to be that guy, but which public companies are likely to benefit financially from the success of these therapies?

I'm not sure what are you trying to really ask...

What companies would benefit from this? All of the larger pharma ones, basically. A large portion of the larger pharma companies have made large investments into the CAR-T space. A company that was spun out of Fred Hutch Cancer Research Center (I used to work there, not in CAR-T though), Juno Therapeutics, was purchased by Bristol Meyer Squibb. Another company in this space, Kite Pharma, was purchased by Gilead Sciences in response to this. And those are just the two off the top of my head that have made large investments.

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