The cancer vaccine roller coaster (2009) | Hacker News Reader

The cancer vaccine roller coaster (2009)

nature.com

40 pointsrsfern28 comments

There hasn't been a huge amount of progress in this area since this came out in 2009 at least from looking at Wikipedia. https://en.wikipedia.org/wiki/Cancer_vaccine

While not a direct vaccine, my best friend was just cleared of most of his cancer with immune system based therapy that didn't exist in 2009.

Is this mRNA therapy?

Probably not. I’m not GP but the most common are known as ‘checkpoint inhibitors’ that attack one of the pillars of a ‘successful’ cancerous mutation: (over)expression of PD-L1, a surface protein that tells the immune system that it’s sniffing a healthy cell (eg. ~these are not the cells you're looking for~). Checkpoint inhibitors work by binding to those ligands, effectively disabling their spoofing action and allowing unhealthy stench of the cell to flow through.

There’s also CAR T-cell therapies which effectively extract and culture T-cells to be more sensitive to the specific disease, then re-introduce them to the patient. These are best for blood cancers.

There’s also monoclonal antibodies and a variety of sensitizers in development and being tested.

We still have a ways to go, but personally it feels like the immune system is the best agent we have for fighting cancer. It’s entire job is to rid the body of pathogens, down to the individual cell/particle, with an adaptivity and specificity we can only dream of in medicine. Aside from the fact that cancers look just like us for the most part, it’s perfectly suited to the task.

The thing I really am looking forward to specifically with the mRNA technology we have today is the ability for a lab to take a sample from a biopsy, identify very specific markers for those cells, and quickly develop targeted therapies for the individual patient. It might be 100 years away, but that feels like the future to me.

>It might be 100 years away, but that feels like the future to me.

I think if it works it's probably quite close now, with how much funding the mRNA scene got through covid. Plagues, wars and famines can often lead to leaps in technology that would have otherwise not worked.

look at the pipelines for BioNTech and Moderna (both of which predate the diversion of their resources to Covid 2 years ago) and you'll find exactly what you worry is 100 years away, already being done. Not kidding.

As for the targeted therapies. This is precisely what started being trialed a few years ago. In people, not just in mice.

https://www.nature.com/articles/d41586-019-03072-8

This is so good to see. Thanks!

Of these the PD-L1 and MABs are the most advanced, a number with FDA approvals and used as standard of care for a few cancers. Side effects can be nasty but often controlled by backing off the treatment or steroids (most problems are the immune system attacking the wrong thing like thyroid, colon, pancreas, etc). They’ve been game changing with nearing 50% success rates for some cancers - hence the Nobel prizes. But that still leaves 50% or more.

mRNA as a platform is really exciting, but most current trials are personalised and very labour intensive, so intake/trial sites are minimal.

I worked with a genetics therapeutic company a while ago, CAR-T is looking to be the future of cancer treatment. Extremely expensive but no long term effects observed thus far. That said, its very early in the process to say it's the "cure to cancer".

"Car-T cancer treatments: From science fiction to saving lives "

https://news.ycombinator.com/item?id=30398672

Very cool. What was the treatment that he got?

The lowest hanging fruit for cancer cures is regenerative cloning. When your body develops cancer, get a head transplant onto a monoclonal, antigenless (ABO, HLA, etc.) body grown in a lab. The only cancers it doesn't solve are of the brain, blood, and head.

Of course we haven't built any of this technology because it's "icky". But we need to get over ourselves. Our bodies are biological machines. Cloning can be done ethically by decephalization genetically or surgically during development, then artificial innervation, life support, and hormonal development. Grow them in pig uteruses at industrial scale.

This approach also solves heart disease, kidney disease, and pretty much everything else.

You get a new heart, set of lungs, thymus... It'd likely increase lifespans dramatically.

You could choose your height, build, gender...

Once it's 20-30 years old and accepted tech, we'd probably even develop transgenic lines with fluorescent hair, increased endurance, magnetoreception, ...

Cancer is hundreds of different molecular breakdowns of different cell types. Changes to adhesion, proliferation, signalling, etc. Lots of different problems. And if we "fix it", we're doing nothing to repair the genes of the cells that directly led to cancer. They'll still be sitting on the precipice of developing it again.

Replace the body.

Growing the replacement body and getting general acceptance is probably channeling itself, but seems easy compared to connecting the “plumbing and wiring” from the head to the body. How close are we to doing this?

Insanely far away if we never start.

I think this eventuality is a little odd, but it is worth at least doing some meta-analysis to see if different parts of medicine would be the best to pursue. E.g. we currently focus a lot on palliative care, accepting that death is inevitable. We need to change that expectation if we're ever going to get life extension technology.

I don't think we can join nerves well enough at the moment. Seems like a problem we'd need to solve first.

Can you even grow the entire human body in less time than it takes for it to grow naturally, e.g. some 18 years?

Maybe not but it only takes 2 years to reach 1/2 adult height. That hardly seems the worst problem - better to (temporarily) be a midget than dead, surely?

But you wouldn't be a midget. You'd be a 2 year old toddler body with an adult head.

Right, better than a midget because you'd be growing rapidly.

Definitely better than being dead.

I've wondered the same thing so I looked it up.

The giraffe gestational period is approx. 15-22months and their newborns are approximately 180cm tall and 68kg.

I wasn't able to figure out what the actual bottle neck in growth rate was, but best I could figure it had something to do with the normal surface-area/volume thing and how it affects nutrient diffusion across the placenta.

If you look at Ancencelphy[0] and the development in artificial wombs[1] you can see that most of this work is simple engineering problems with the nerve reattachment being the only R&D stumbling block that remains.

I honestly think that we could solve this problem in less than 10 years if we approached it as it were a moonshot or a mRNA covid vaccine.

[0]https://en.wikipedia.org/wiki/Anencephaly [1]https://www.sciencealert.com/researchers-have-successfully-g...

Until we fully understand the human body, down to the level that we can decode thought by observing brainwaves, we don’t really know that bodies are biological machines. For all we know the body could be a form of antenna for energy/physics we don’t yet perceive or understand. It’s important not to assume our current understanding of science defines reality. It’s our best estimate.

1) Modern machine learning models like GPT-3 exhibit properties of human-like intelligence despite using no magic. Occam's razor would tell you that human intelligence is also due to the enormous number of neurons and their connections.

2) This hacker news article is relevant: https://news.ycombinator.com/item?id=30350261

If we're going to compare human beings to radios, I'd say it's far more likely that some part of the body is the case of the radio while the radio is contained within it. If the body is acase for the radio it makes no difference if you swap it out.

I'm willing to accept that my brain is an antenna for consciousness from another dimension but I find it hard to swallow that my toe nails are as well.

Primarily the brain, absolutely. I’ve read the illusion of conscious will and similar books. They struck me as overconfident drivel. We do not understand the universe on a macro or micro scale, and there are just to many oddities for me to dive head first into contemporary explanations of consciousness presented as “fact” by narrow minded “experts”. A physical computer view of the brain could just as easily be an antenna, and damage to either could still cause the observed issues from brain damage, psychological disorders, etc.

A great example to dive into is the phenomenon of crystal polymorphism; specifically, how the primary crystalline form of a chemical changes simultaneously at labs on the other side of the world with no cross contamination. It’s a huge problem for pharmaceutical companies, but the interesting part is that there is no rational explanation for the phenomenon presented by modern science.

Science is based on observable fact, but where humans go off the rails is making the assumption that everything is observable, that observations are sufficiently precise, or by dismissing new ideas out of the narcissism of being an “expert” in a competing theory. It’s a theme that repeats over and over again throughout history.

I think it is entirely possible consciousness could be a related to a force we do not understand or even perceive, similar to crystal polymorphism.

This is the theme of a Greg Egan short (is there a scenario that guy hasn't come up with? Truly an SF beast). The body is grown at an accelerated rate with a relatively "dumb" brain. The brain has the capacity to carry out normal bodily functions and not much else. After a year, the original brain is transplanted into the body.

That said, this is more like "very-hard-to-reach golden fruit", not low-hanging fruit.

There is a lot of hype behind mRNA as the next step in training the immune system to fight cancer. I hope it works

mRNA for Covid was built on what was learned from trying to use mRNA for Cancer. I personally think mRNA is going to really help a lot of people in the future.

My kid passed away at 12 from Bone Cancer and my sister (not biologically related to my son) died from brain cancer qat 15. There is no treatment for Bone Cancer that actually makes survival any better in the past 35 years. This is a potential first treatment that might change the percentages for kids and adults. https://www.frontiersin.org/articles/10.3389/fmed.2021.64261...

Kid Cancer cures requires a lot more time because kids' cells are always growing are much harder to come up with safe treatments. There was a 20+ year time when not one new chemotherapy was used to treat kids till St. Baldrick's funded research finally introduced something new for kids. If we get something that works on Adults it will take 10+ years to go to kids. If it works on kids then the research will help adults in a year or two. That the world focuses 90%+ on adult cancers is very frustrating.

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