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Comment by rubatuga | Hacker News Reader

Immunology is one of the biggest fields that are stepping up to fight cancer. In a nutshell, we are programming the patients immune system to kill its own cancer cells, a marked departure from the general toxic chemotherapy that weakened almost every dividing cell in the human body. I believe people in a few decades will look back and express disbelief at the barbaric way we tried to treat cancer.

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Well, the flipside is that if you stop chemo, the damage to your body stops.

But if the immune system over reacts, it can run out of control and kill you.

I have a relative with stage IV melanoma. She was included in a research trial that used a pair of immune stimulating drugs in an attempt to get her own body to fight the cancer.

What they didn't realize is she had a latent, undiagnosed autoimmune condition called vasculitis.

Unfortunately, while vasculitis is normally isolated to a particular part of the body, hers was systemic. What followed was an immediate halt of the drug regimen and massive doses of steroids to get it under control. If that hadn't have worked, it would have killed her. Full stop.

The condition is now fortunately under control, but she has 30% kidney function, and the steroids pushed her over to full non-insulin-dependent diabetes. She's now on a targeted therapy that, for now, has pushed her into full remission, but it's only a matter of time before the melanoma becomes resistant to the drug.

The reality is, doctors do not fully understand the immune system. Period. These treatments are in many ways astonishing, but they can turn frightening very very quickly. And they don't always work, either.

Unfortunately, there are no miracles, here. Not yet.

That's true, but assuming this specific treatment doesn't reprogram the native immune system, it sounds like the side effects are much shorter and less devastating than the systemic damage of chemo, even if requiring repeated attempts.

Well, given the doctors in the article flat out stated that:

There was a chance that his immune system would go into overdrive, and there was a chance that the edited T-cells wouldn’t be as potent as they expected. The medical team just really couldn’t be sure what would happen.

That article goes on to note all manner of side effects with this style of therapy: fever, tremors, convulsions, encephalitis... and right at the end we have this quote:

He had an atypical skin growth, a chronic cough, a sinus infection, a puddle of fluid at the bottom of his lungs, a virus in his right eye, and bad heartburn.

Of course, as far as side effects go, this is pretty minor. But there's no understanding of why these types of things happen in the first place because our understanding of the immune system in vivo is just not very good.

or express disbelief that we didn't anticipate <fairly obvious outcome> as an unexpected side effect of immune system tailoring.

<fairly obvious outcome> is likely to be "large increase in incididence of autoimmune disorders"

Which might be controlled by immune ablation; safer targeted forms of destroying all immune cells would be a very good way to stop all forms of autoimmunity, and would act as a good backstop to immunotherapies in general.

Right now immune ablation is pretty rough chemotherapy, but has nonetheless been shown to put multiple sclerosis and type 1 diabetes into remission. There are new approaches to targeted cell killing under development now (such as Oisin Biotechnologies' system) that should be much better, with minimal side-effects. Couple that with a cell therapy to accelerate replacement of immune cells and it looks pretty promising.

Well if you use antibodies, they should be able to slowly be excreted and broken down after a while. I don’t believe antibodies undergo any memory effect. If you use a specific form of T cells, they should undergo the same degradation, although I guess there is a possibility that in some unknown cases it might revert to a memory cell, although to my knowledge this doesn’t happen. Lastly, since the virus used to express the receptor should only infect the cells extracted from his blood, any autoimmune response shouldn’t last (since cytotoxic T cells don’t last forever). The virus isn’t self replicating, and isn’t used to infect any other cells.

thats a lot of "shoulds" for a complicated system.

I don’t believe you have a compelling argument, any biological organism has a degree of unpredictability, but with a series of molecular checks and controls, it becomes predictable, almost deterministic. Think of how the brain works, how you have billions of cells acting the way they “should”, and acting in a predictable way allowing you to perform daily tasks. I agree we have a lot to learn and that some mistakes might be made, but that’s what testing and clinical trials is for.

Unfortunately, autoimmune diseases violate the assumption that biological organisms become also predictable. That's true for brains, too.

I'm not sure "barbaric" is the right word. It's ugly and unpleasant, but it works and it's the best hope we have for many people. "Barbaric" to me would be bleeding a patient to balance their humors; chemotherapy is more along the lines of amputating a septic limb.

I would like to see a more elegant means to boost the immune function, without so much of the Dr. Frankenstein element. I think supporting the immune function is the way to go, but I think we need a lighter hand, not a heavier one.

If you are directing the immune system against cells that the body perceives as 'self', then simply boosting the system to the point it attacks a cancer will likely be detrimental the patient. Cancers and other similar diseases are so difficult to address precisely because they are borne from a patient's own cells, own genome, and own systems. This therapy here is a very pointed mechanism to demonstrate to the immune system what is okay to attack, and what is not - a very particular and specific kind of guidance that a generalized 'boost' would not properly address. And in that way it actually is an elegant, precisely designed system in play here.

Cancers and other similar diseases are so difficult to address precisely because

My general understanding is that they are so difficult to address because we don't really understand them.

I have a condition that gets partly explained as "overactive immune response." I really hate the concept of autoimmune diseases and I hope that someday it will be mocked as "god, what those barbaric idiots believed back in the day."

'Cancer' is a huge umbrella term. Some cancers we know very well, many we do not. The one's being addressed by these therapies are well enough understood to target therapeutically. Some like cervical cancer, skin and lung cancer are well enough understood to in part be prevented.

But under that umbrella the reason cancers are 'hard to treat' (from the perspective of a pharmaceutical education/industry/knowledgebase that had a century of success curing invading diseases) is because cancers do not present a 'differnece' that can be exploited biochemically. Cancers are by definition a mashup and amalgamation of the components that make up a human - again very much unlike a bacteria, viral or fungal infection.

You are correct though that there is still a lot for us to learn. The technologies in this article are very much a glimpse of the next steps though.

That honestly does not fit with my understanding of the problem space. Granted my understanding of the problem space is as a layperson, not a medical professional. But I am a layperson who took care of a relative after their first mastectomy, I have multiple relatives who have had cancer, some of them repeatedly, and one relative was themselves Patient Zero in a cancer treatment study. So, it isn't like I have been unexposed entirely to the intricacies of cancer treatment.

I don't really know how to effectively engage you, but I stand by my initial statement of:

I don't really feel you are making points that invalidate that desire. Perhaps we just don't understand each other. If so, it is probably best to stop here rather than keep digging a deeper grave.

Overall, one of the simultaneously amazing and depressing things about modern medicine is that treatments that were the gold standard only a generation or two ago now look as barbaric as leeches and bloodletting (leeches are back in vogue, anyway).

Considering that by some measures we have made hardly a dent with our 40-year war on cancer (https://blogs.scientificamerican.com/cross-check/sorry-but-s...), I feel confident that this is but the start down the road of immunotherapy.

I agree. On the other hand, at least now we have something that seems to mostly work, and that's a good start.

what on earth is your objection?

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