Man in remission from blood cancer and HIV after remarkable treatment | Hacker News Reader

Man in remission from blood cancer and HIV after remarkable treatment

theguardian.com

200 pointsTeever55 comments

These sort of articles pop up every few months and make people hopeful for a cure, but this is sadly unlikely to ever be a viable one.

Stem cell transplantation is a standard treatment for several blood cancers, but will almost certainly never be a standard HIV treatment for anyone except patients who need a transplantation anyway, for one single reason: with modern medicine, living with transplanted stem cells is significantly worse than living with HIV.

With modern meds, HIV patients can have a normal life expectancy and live basically normal lives.

You know how in traditional organ transplantation, your own immune cells will attack and often destroy the transplanted organ? In stem cell transplantation, your transplanted immune cells will attack every single organ in your body. Look up "graft versus host disease."

After stem cell donation, most patients will have to take immuno-suppressants that a have significantly worse side effects than modern HIV meds do, often for the rest of their lives - and that's the lucky ones, where the meds will successfully treat the graft versus host disease. One of the more gruesome sights I've seen in my medical career was a lady with a severe graft versus host skin reaction that her doctors couldn't get under control despite massive doses of immuno-suppressants. Eventually large parts of her skin peeled off in strips, like something out of a horror movie. Then she died of pneumonia from the immuno-suppressants.

This is an extreme example, of course, and many people live perfectly ordinary lives after stem cell transplantation, but the failure more is both more likely and more gruesome than the one for antiviral HIV treatment.

This is correct. I have an extremely rare leukemia <1 in 100k, and as said above, the only cure is allogenic marrow transplant. To put it bluntly, survival is at best a 2/3 dice roll - and that's if you're diagnosed before 40.

This is not something you're going to want for something as apparently treatable as HIV.

I hope your die falls on one of the 2 good sides.

The avenue towards making this a viable, routine cure for HIV is by performing a “transplant” of the patient’s own immune stem cells that have been genetically modified to carry the anti-HIV genes. That avoids (if done right) the horrific autoimmune challenges you describe, but like everything else it comes with its own technical challenges that are still being worked out. (I think https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4935568/ is a good review of the whole idea.) To me (though I’m not an HIV researcher by any means!) this sounds like the most promising shot we have at regularly curing the disease.

This seems like a little bit of a fearmongering. We're slowly understanding GVHD and GVT issues, suppressing one while keeping the other. The frequency of GVHD has been going down over time as we better match donors to the patient.

There are a lot of treatments that started off just like this. For things we thought we would never have a proper cure for, until we gradually understood how treatment worked and how to refine that treatment.

Not the same as large-scale transplantation, but that reminds me of some work in Chimeric Antigen Receptor (CAR) T-Cell therapy, where the dangerously-useful cells either have a manual suicide-switch or else another method to temporarily deactivate/reactivate them.

So still sci-fi at this point, but I'm imagining some kind of "bone marrow in a box" implant which cages the borrowed immune-system (copied, rather than genetically-engineered) within a barrier that somehow allows only roaming/non-reproducing cells to exit.

>but this is sadly unlikely to ever be a viable one.

I'm not a medical expert by any means, but you claiming this is unlikely to ever be a viable idea makes me think of the sheer number of things we take for granted today in medicine that to a 19th century or even an early 20th century doctor would seem flatly absurd, or completely incredible. A supposition of never makes a bet that one's own limited frame of knowledge, cognitive capacity and imagination has a leg up on all the potential decades ahead of us worth of new discoveries by a vast number of other very clever people. It' s a bet I wouldn't make in my own favor or anyone else's.

Don't we just need to induce new stem cells from the patient's own cells, and transplant those in?

Edmonds, of Desert Hot Springs, California, underwent a treatment in which he received stem cells with a rare genetic mutation that makes people who have it resistant to acquiring HIV. The stem cell transplant came from a donor with the rare homozygous CCR5 delta mutation.

Here's a dumb question: is it possible to culture stem cells? Or make more of them? Or does every stem cell have to be donated?

The process is commonly known as stem cell culture or stem cell expansion. Stem cells have the unique ability to self-renew, meaning they can divide and produce more stem cells while maintaining their undifferentiated state.

You can build stem cell lines that reproduce stem cells.

You can also "go backwards" from skin stem cells to fully featured stem cells.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3584308/

>Induced pluripotent stem (iPS) cells, are a type of pluripotent stem cell derived from adult somatic cells. They have been reprogrammed through inducing genes and factors to be pluripotent. iPS cells are similar to embryonic stem (ES) cells in many aspects.

You can even do it without 100% causing cancer now.

here's a breakdown of the current progress in a chart.

https://www.lifespan.io/wp-content/webp-express/webp-images/...

Not a dumb question at all. The difficulty with cells from multicellular organisms is that they are used to be part of a larger organism. Isolating individual cells and keeping them alive is very difficult.

The oldest cultured human cell line are HeLa cells[1] which are derived from cervical cancer cells and they are therefore not normal human cells. Cancer evolves to be resilient and is therefore easier to cultivate than regular well-behaving cells.

[1] https://en.wikipedia.org/wiki/HeLa

And another one: could we take someone's own stem cells, edit this mutation into them with CRISPR, culture more of them, and then re-implant them?

Yes in theory. However there is a lot of tricky parts that mean we are not doing this in real humans often it at all.

Yes, example: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10418799/ although I am not sure if T cells are considered stem cells or derived.

Yes, there are approved treatments that do exactly this with stem cells for some diseases.

you can also collect cord blood just after birth of a baby. The blood contains stem cells that will be compatible with your baby and possibly other people in your family. Might be useful one day

Induced pluripotent stem cells (iPS) were a major development by Shinya Yamanaka around 20 years ago. Essentially, you take an adult's cell and induce it to become a stem cell.

I don't know much more about it but that certainly is part of the answer to your question. Hopefully others will chime in ...

Also sounds like you could create a human clone embryo and harvest the stem cells.

There are already surrogate pregnancy outsourcing places in poor parts of the world - if this is viable I expect this to become the new blood boy fad for the rich.

Are these sorts of treatments available anywhere in Europe?

On our underfunded government socialized healthcare systems? No way.

Those who are minted go to the US or Switzerland for best cutting edge treatments and prosthetics.

>> On our underfunded government socialized healthcare systems? No way. Those who are minted go to the US or Switzerland for best cutting edge treatments and prosthetics.

Switzerland is a European country.

They probably mean EU

>Switzerland is a European country.

Without the socialized healthcare system I was talking about.

Only 5 patients worldwide has had this dual treatment so far, as far I understand - it's experimental. There's basically one clinic running tests on this specific treatment.

Stem cell treatments for this kind of cancer, however, is on the UK NHS's list of treatments when the first line treatments do not get an optimal response, and from what I can see they've been in the guidelines since at least 2020. Given the NHS is one of the "cheapest" (as in stripped of cash by successive governments) socialized systems in Europe, if the NHS can afford it, lots of others can too.

It's not the first choice for most patients because it is not suitable for everyone.

The second patient to be cured this way was from London.

This procedure was first used about a decade ago in Germany.

I believe its a byproduct of stem cell transplant treatment for blood cancer combined with the luck that the matching donor having a mutation that protects against HIV.

It’s not “luck”. They specifically look for such a donor.

Stem cells seem to have this potential to cure so many things but we are somehow not there yet.

Are there still laws in place that prohibit research using stem cells? That might not help

Most of those only impact ESCs ("Embryonic") and not ASCs/iPSCs ("Adult"). There is plenty of research that can be conducted even in those places.

Some highlights after reading the Wikipedia article on Stem cell controversy:

- Austria, Denmark, France, Germany, Portugal and Ireland do not allow the production of embryonic stem cell lines

- The creation of embryonic stem cell lines is permitted in Finland, Greece, the Netherlands, Sweden, and the United Kingdom

- Arkansas, Indiana, Louisiana, North Dakota and South Dakota have passed laws to "prohibit the creation or destruction of human embryos for medical research"

- China has one of the most permissive human embryonic stem cell policies in the world. In the absence of a public controversy, human embryo stem cell research is supported by policies that allow the use of human embryos and therapeutic cloning.

- The Catholic Church opposes human embryonic stem cell research calling it "an absolutely unacceptable act." The Church supports research that involves stem cells from adult tissues and the umbilical cord, as it "involves no harm to human beings at any state of development."

- Islamic scholars generally favor the stance that scientific research and development of stem cells is allowed as long as it benefits society while causing the least amount of harm to the subjects.

my understanding is that embryos aren't the primary source of stem cells anymore and all of these jurisdictions are satisfied

Miqu 70B Q4_K_M writes

Embryonic stem cells are one of the main sources, but not the only ones. Embryonic stem cells are derived from embryos that are 3-5 days old. These cells have the ability to develop into all cell types in the body. However, due to ethical concerns and the limited availability of human embryos, researchers have also developed methods to create induced pluripotent stem cells (iPSCs). iPSCs are adult cells that have been reprogrammed to behave like an embryonic stem cell. They can be generated directly from adult tissues, such as skin or blood cells. Another source of stem cells is the umbilical cord blood and tissue, which is rich in hematopoietic stem cells. Adult (or somatic) stem cells are also present in various tissues in our body, such as bone marrow and fat.

and here is a wiki and non-wiki source I found on iPSCs just in case the LLM made up an acronym. https://en.wikipedia.org/wiki/Induced_pluripotent_stem_cell

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3347549/#:~:tex....

(this is how I do most of my queries these days)

California legalized stem cell research ~20 years ago, https://www.nytimes.com/2002/09/23/us/california-law-permits... This led to CA being one of the world leaders (funny that a state can be a world leader, but that's CA in a nutshell) in stem cell research and applications.

I worked in a few labs that did stem cell work and we got really attached to some of them. Like, "here's a microbrain I've been growing for 3 months", you start to empathize with them a bit.

The reason that whole controversy basically evaporated is that embryonic stem cells have so far been useless - anything you can do with them can also be done with adult stem cells.

As far as I know there is no treatment, or even research that requires those cells vs adult ones. It also helps that there are embryonic cell lines available commercially, with no restrictions (in the US), for those who want to specifically study them and not adult ones.

So to answer your question: No, the laws are not harming anything.

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