(The article blithely says "remissions measured not in extra weeks or months of life, but in lifetimes". It's a little over-reaching since we just don't have that much long term data yet; these therapies haven't been around for "lifetimes". As a result we often prefer the term "durable remission" to "cure".)
I also want to emphasize how few patients have this outcome. It sucks. It sucks to have ads on bus stops and TVs that say, "Ask your doctor about Keytruda", but when they ask me, I know it has such a tiny chance of turning them into that laughing family playing in the grass. We test for and hope for the genetic markers that indicate certain immunotherapies are more likely to work spectacularly, but the vast majority of patients don't have those markers. Similarly, most patients with leukemias or lymphomas do not respond to CAR-Ts.
We still try these immunotherapies, though, because there's often evidence of some modest better outcomes, and also sometimes you get lucky. I think I mentioned this on HN in some other context, but one of the breakthrough discoveries around pembrolizumab was because of a "Hail Mary" in late stage colorectal cancer; all the patients progressed & died in the study except for one, and she held the key to the genetic derangement that made that subset of cancer particularly sensitive to checkpoint blockade -- leading to FDA approval for pembro for all cancers with that derangement. As this article mentions, there is now a massive number of trials studying these therapies in various subsets of patients, or in various combinations and permutations with traditional therapy, because short of "cure" there's still improved survival which can often be very meaningful.
It's exciting. It's inspiring. It's frustrating & heartbreaking.
Without the possibility of trying this my options would probably be dying slowly over the next couple of years or doing a very risky surgery that involves opening up my abdomen, cutting out as much of the disease as they can see and flooding the cavity with broad spectrum chemo (HIPEC.) Obviously, immunotherapy is much more palatable as the chemo was not pleasant.
Overall I am hopeful. I guess I don't really have a reason to post any of this, other than it helps to get it out there, so please excuse my rambling! And thanks for reading.
I know that feeling well. Best of luck to you.
Oh, and Fuck Cancer.
I'll spare you the cliches; we all know people that died of something (or are dying of something). But it is very heartbreaking to know about people suffering right now when the cure for what is killing them might be just around the corner.
>> Schmid said: “Immune therapy on top of standard chemotherapy prolonged survival by ten months
Since, I guess, patient are interested by "being cured", how should I interpret those ten additional months? Of course, I understand the statistic behind it, but I' d like to know if it translates to something meaningful for the life of the patient. For example, if I had a ten month increase in my life, considering that it could mean live 10 month more with
pain, false hopes, etc., then I wouldn't feel that the situation has improved meaningfully (of course I don't have cancer and therefore I may miss some obvious benefits).
OTOH, if that increase means that the chance of long time remission also increase, then, that's a whole different situation...
Situations are complex and outcomes are highly varied. One size does not fit all.
We do not know if there is a meaning to life. But on a human level we are connected through social connections and these people who are connected to us can give life a meaning on some level.
I also disagree that death makes you no longer care. Yes, you as a person supported by a mortal body will no longer feel anything. But the concepts that made up your personality and the actions you took while being alive will still influence the events in the world. You cannot react any more, but most people at least define a written will for the time after they are dead. Just take the nobel prize. It is based on a will that wants to shape the world for the better long after the body of Alfred Nobel has died. The nobel prize is still going strong.
The fact that the rest of one's life is "short" compared to someone else's does not mean that it's less subjectively meaningful.
You can't bet just 50% on nihilism. Either go all in or acknowledge that people want to have as many positive experiences as they can, no matter how much time they have left.
What you’re talking about is the opposite, turning the T cell “off”. You’d also need to do that to every T cell or alternatively, destroy every T cell and restart with a batch of new cells.
Very different problems.
But, there's hope for other diseases, though the article is focused on cancer:
> Not only can this technology help revolutionize TCR-T cell therapies for cancer, but it will also be a powerful tool for discovering other immunological agents, including antibodies and CAR-T cells, and for elucidating new immunology and cancer biology at a depth not possible before.
I guess you’d need to design some kind of exfoliator to get enough skin. I told you it sounds ridiculous.
So, no, I don't think so. To theoretically transfer a distinct marker to all cancer cells, you'd need a distinct target in the first place.
Radiation has gotten extremely good at being far more targeted. The doctors actually model the absorption curves and let computers target the specific areas to make sure that the specific area gets the necessary dose while keeping the dose down in the surrounding tissue. If you can do radiation, it is by far the best option nowadays. Sadly, you can't always use it--sometime surrounding tissue is too sensitive to radiation (intestines) and sometimes things are simply too large.
Chemotherapy, though, just really, really, sucks. Almost anything is better.
So my question is when we donate to cancer research, are we donating to public research or are we handing our money to a for-profit corporation. What is the path from donation to six figure cancer treatments? I would be very interested in how that works.
In the US. 
If we want to increase the rate of return on investment the big, easy win would be dropping the efficacy test. If we want to reform the system of funding altogether buy out patents for their market value or give massive prizes and then have the drugs freely available for anyone to manufacture.
An interesting approach is the cystic fibrosis association in the US that directly invested in a new CF drug. They made a ton of money and rolled it back into research.
The overall issue you're speaking of is the healthcare system in the US, which is not present in other countries where drugs and treatments may be present, albeit slightly delayed, for much cheaper. Some of the most expensive options are biologic drugs, which cost a lot but that's because they are more difficult to manufacture and are often tailored to the individual patient level.
Still, the US healthcare system is supporting the main engine of biotechnological research in the world. Look at Cambridge, MA and you will see huge brain drain and financial investment into pharma and biotech companies.
Typically the way it works today is that an academic group, startup or big pharma company will have a "seed" of an idea for a drug. Some of the early drug discovery work happens in academia, some in startups, some at big pharma. But by the time that a potential drug enters preclinical development it is almost always owned by a for-profit company because they have the budget and resources for this work. At this stage fewer than 0.01%-5% of candidate drugs end up working and getting approved by FDA, and it costs tens or hundreds of millions to get a drug approved (and it can cost multiples of that if you include cost of failed drugs). So these companies take a tremendous amount of risk.
These days startups do most of the late stage discovery / early stage development work. They often take the drugs through the riskiest phases of development, generally up to Phase 1/2 or Phase 2 where effectiveness is first tested in humans. Phase 2 failure is the single largest driver of the cost of drug development. Phase 2 failure rates are as high as 60-70%, and it can cost $100M+ to get a drug to Phase 2.
In many cases a startup will try to sell their drug to big pharma after good Phase 2 data. At this point the risk is much lower (drugs have a better than 50% chance of getting approved), but they require significant funding to do the large Phase 3 studies needed for approval and to fund commercialization (can need 9 figures just for Phase 3 work and submission to FDA). So at this point it is a lower risk / lower return bet, but an expensive one, and big pharma companies are structured to take those bets.
However big pharma companies also spend a lot on early stage R&D. From looking at SEC filings, it seems roughly half of big pharma R&D is early stage and half late stage. The problem is that big pharma typically does not do well at early R&D. The return on investment in R&D at big pharma companies is approaching 0%.
Much of the high price of drugs is simply a function of the high risk and high cost of drug development. Very few drugs that pharma invests in actually become profitable drugs. So they try to milk all they can out of the few winners. It isn't the case that pharma's business model is buying fully derisked products from academia and then jacking up the price.
And while at some point publicly funded research could replace for-profit research, the reality today is that if we didnt have for-profit drug research then we would not have new drugs.
in 2017 the FDA approved 49 new drugs. None of those were owned by non-profits at approval (one was owned by a public-private JV). There is not enough non-profit money to take drugs through the development process to FDA approval
And when high prices do exist, in many cases it is because the drugs literally save lives. If you value a QALY at $50K / year (a common estimate), and your drug enables a child to live a full life who otherwise would have died at age 2 due to a rare genetic disease, it doesn't seem absolutely crazy to charge $1M for that drug. The issue to me seems to be more 1) what happens if you pay $1M for a drug and it doesn't work or 2) what if the patient cannot afford to pay $1M upfront for the drug even if it is guaranteed to add 20 healthy years to your life.
> if we didnt have for-profit drug research then we would not have new drugs.
I don't think that follows. If we didn't have for-profit drug research, we would have less volume of safety and efficacy testing and data on drugs, but we would still 'have' the drugs.
I think drug testing reform must be part of the solution. Bringing a drug to market is too expensive.
Pharma companies don't just run clinical studies. They do a massive amount of discovery work and preclinical development, probably on the order of $100B worth / year
I do agree that drug testing reform can play an important role in lowering the cost of drug development. Things like not requiring cardiovascular outcomes studies for diabetes meds would be a great start, and providing clearer guidance for development of complex generics. However i dont know what else might be done that wouldnt compromise the quality of approved drugs, a lot of the difficulty is just our limited ability to directly study human biology
> Hype can be dangerous, just as false hope can be cruel.
I would therefore suggest reading the last two paragraphs carefully.
I have ulcerative colitis and am on immunosuppressants. So I'm more likely to get cancer and can't get that treatment.
One of several studies we reference when we treat these patients: https://www.ncbi.nlm.nih.gov/pubmed?term=27687304
What's interesting (and increasingly being studied) is the higher risk of developing an autoimmune condition after treatment with some of these immunotherapies. The absolute risk doesn't seem to be huge, but it's an interesting window into how these conditions might develop in the first place.
The primary tumor isn't packing up and migrating, it is rooted in place like a tree. A cancer cell circulating through your body doesn't seek to get to the lung, it just might happen to end up there and it might grow well there and form a new tumor, like an acorn falling off a tree. Some acorns will fall into rich soil, some will fall on pavement or get eaten. You can't coax acorns to fall squarely into your bucket, and even if you did you still have the tree to deal with.
Honeypots only work when there is consistent attack pattern to detect, and a means to mitigate that attack. But with cancer, getting a tumor to grow in one kind of cell will not prevent a different kind of cancer from developing in a different kind of cell.
We can "manage" cancer without understanding the root cause. We cannot cure it.
The thing is, a single cancer cell is not a problem. The problems really start, once the cancer cells creates a great number of copies of itself and disrupts the operations of the other normal cells.
What makes cancer tricky, is that cancer cells still are derived from normal cells and they might look too similar to normal cells so that it is difficult for the immune system to spot and kill them.
What is now the root cause? The root cause is errors in the DNA sequence that accumulate over time. This is a natural process. The cells have some DNA repair mechanisms, but they are not perfect. To fully cure cancer, you would need to correct all DNA sequence errors which is not practical. However, in practise, this is not what is needed. Instead, it suffices if the cancer cells are being killed. And our immune system is pretty good at this. But at some point, some cancer will have a faulty DNA seuence, with new program code, that helps it hide from the immune system and then we need the help of doctors to get rid of the cancer.
Over all of those trillions of cells and dozens of years, once in a while, a particular cell gets just the right batch of random mutations that make it possible to stay alive while breaking free of its programming and acting as its own organism, independent of the body's plan. It may then proceed to reproduce on its own, potentially disrupting the body's functions and/or consuming all of its resources if it grows quickly enough.
So each individual cancer case is a uniquely evolved life form. There's a few common threads that many tend to share, but no telling how many each particular case may have. Thus, the broad brush approaches tend to be the most successful - surgery, chemotherapy, and radiation. More directed genetic approaches are tougher because of the uniqueness of each case.
Evolutionarily, it's a tricky balance. Too few mechanisms to keep all of your cells under control all the time, and your body dissolves into a mess of cancers too soon, like before you can reproduce. Too many mechanisms wastes resources, can potentially go haywire and damage your body themselves, like autoimmune diseases, or make it too hard for your body to evolve new and useful adaptations to the environment. We already have good enough controls that getting cancer before normal reproduction age is very rare. But now we're living a lot longer, much longer than our bodies are evolutionarily adapted to keep us alive for, so we see a lot more of these kinds of problems.
If living beyond the age we were designed for is the cause, I wonder why the American Cancer Society says:
By 2030 the incidence rates among people ages 20 – 34 years will increase by 90% for colon cancer and by 124.2% for rectal cancer.
In that case, either we are engineered badly (genetic) or there are factors that cause cells to go rogue (epigenetic). We still need to find the root cause.
I have a hard time believing there are faults in the way we are designed.
People are working on ways to end cancer. Aubrey de Grey has a plan which, unlike his others for fighting aging, I think is totally crazy but hey at least someone is working on it. But its certainly not something that could evolve in nature.
Likely a result of letting their niche be taken by descendants made them more adaptable than ones which lived until other constraints or more or less bad luck (cummulative fatality risks over time) killed them.
We just released a browser-based client to assist users not comfortable with constructing the long and complex command-line arguments used with most bioinformatics analysis pipelines. It also provides a REST API that makes it easier to integrate into existing research/clinical pipelines.
If you're working in this area of research/treatment please check it out to see if pVACtools can be of use to you!
EDIT: Just received a writeup in GenomeWeb:
* as a user-interface designer/developer
Am just interested bc i have a few friends involved in neoantigen / shared tumor antigen cell therapy companies, and did some consulting work for a company that had tech for delivering nucleic acid therapies and was considering getting into oncology, but didnt have in-house sequencing or antigen identification expertise. Mostly intellectual interest at this point
" “The tidal wave of data is still teaching us fundamental concepts about the interaction of the human immune system and human cancer.” "
So, if they still learning fundamentals. -> impact of actions based on inaccurate or incomplete knowledge, is unknown.
in programming this kind of practice would lead to bugs / undefined behaviour etc. - imagine what kind of shit that would mean for human health...
It'd be nice if they had cancer prevention studies instead of cancer cure studies. kthx
Of course the bug could be in proprietary software your code is using. How would you fix that by purely looking at your own code?