Five years ago, I had my own immune system rebooted to (so far) eliminate my Stage IV melanoma cancer in a trial at the National Institutes of Health. At that time, without further treatment, I probably had six to twelve months to live.
In essence, the tumor infiltrating lymphocytes (TIL) adoptive cell therapy was as follows:
1. The doctors removed a melanoma tumor that was growing in my neck.
2. In the lab, white blood T cells (T lymphocytes) that were attempting to attack the cancerous tissue in my tumor were isolated into at least five different petri dishes. The white blood cells' growth was stimulated using IL-2.
3. Those samples that grew the most and attacked the cancerous tissue (2 of the samples, in my case) were then expanded to a total of 130 billion lymphocytes in the lab.
4. I returned to NIH for a week of immune system preparation, specifically the almost complete suppression of my own active immune system using harsh chemotherapy. This was to allow my body to accept the new lab-grown immune system.
5. Once my immune system was sufficiently suppressed, I received all 130 billions of the lab-grown lymphocytes. The immune system was then stimulated by having five large doses of IL-2 every eight hours over a two day period. (Note: This was hellish.)
6. After a week or so, my immune system had recovered and I was released from the NIH Clinical Center to return home. I was given an anti-biotic to take for 4 to 6 months to reduce the possibility of contracting a specific pneumonia (PCP).
7. I returned to NIH monthly for scans monthly for the first three months. After month one, my tumors had shrunk 33%. After month two, 66%. After month three, they were almost complete gone. My immune systems had essentially been immunized against some of the mutations contained in my cancerous melanoma cells.
8. I was declared NED (no evidence of disease after 15 months) and a complete responder to the treatment after 21 months.
Now, almost five years post-treatment, I have had CT scans and brain MRIs every six months with still no signs of melanoma. My doctors have told me that I'm likely cured.
Immunotherapy works. I chose this trial because the I liked the fact that my own immune system was being boosted to fight my cancer.
Also, besides the overall success of my treatment, other than regular followup scans, I don't require any further medications of any sort. It's a one-and-done treatment. I'm certain that Big Pharma doesn't like these treatments.
Congratulations on a successful treatment! It is so wonderful to hear stories like these. Immuno-oncology is bringing great hope to mutation-rich cancers like melanoma.
>I'm certain that Big Pharma doesn't like these treatments.
You would be certainly wrong on that part. Immuno-oncology has been "Big Pharma's" major focus for the past 5-10 years, inspired in no small part by the work of Rosenburg and many others. One of the most recent approvals discussed on HN was for a CAR T-cell targeted against CD19. Big Pharma would also be very happy to sell immune checkpoint inhibitors for use in combination therapy with adoptive cell transfer.
I hope that I'm wrong. Many more patients can possibly be saved with more widespread use of this treatment. Of course, the FDA needs to modernize their own approval processes to deal with such personalized treatments. It's my understanding that my lab-expanded lymphocytes needed to be individually approved by the FDA.
I do know that my specific trial at NIH was sponsored by Lion Biotechnologies as part of that company acquiring a license to reproduce the laboratory processing for the TIL ACT.
Yep. Novartis' new CAR was recommended for approval last week. ~100 are in the FDA pipeline, and now that the first was unanimously approved, expect a lot more.
I have had two melanomas so far luckily for now early stage. I am lucky to be treated and checked by one of the best at Sloan Memorial, but with more than a thousand moles my doctor told me to expect to get more.
I really hope if we don't catch one of these in stage one that I will be able to get treatment like yours.
With regards to big pharma as far as I understand the problem seems to be a little different namely that it's not a pill or a treatment as such but a combination of things which means big pharma wont necessarily be investing heavily in it as they can't turn it into a product (again as far as I understand).
Last but not least. Congrats on the lucky outcome.
At $300,000 each (from the article) I think they and their shareholders would offer it gladly. How many Viagras do they have to sell to match that revenue?
The price in Australia is AUD$30 (~USD$24) for a 12-pack of 100mg tablets [1]. That's totally unsubsidised, although you do need a prescription. How on earth could they literally cost thirty times more in the states?
I used to work at the National Cancer Institute (tumor immunology research in liver cancer). I've met Dr. Rosenberg a number of times -- everyone there wonders if he'll get a Nobel Prize for his discovery of IL-2.
It's really cool to see the patient's side of the journey though - and I'm very glad things turned out well for you. Thanks for sharing :).
Won't the cancer cells mutate again after it figures out that the immune system is working successfully against it ?
If they won't mutate why can't the body choose the white blood cells which are effective against it and amplify them ? Why does it have to be done externally in a lab ?
If they do mutate again, what makes this treatment effective ?
Excuse me for the basic questions,I have no experience in Biology or how antibiotics work.
Our immune system is a force to be reckoned with for any cancers - we don't have figures on how many cancers our immune system clears before it meets one it cannot clear.
So for cancer to survive, it has to thwart our immune system somehow, and one of the ways it does this is to use signalling pathways which dampen down the immune response. It communicates to the cancer 'calm down, don't call your friends'. The immune cells don't go away - instead they switch to a mode where they control rather than clear the cancer.
Adoptive TIL therapy (which is not the same thing as the article is talking about, though they are both T cells) takes the immune cells from the cancer. These cells recognise the cancer as being foreign ('non-self') and in need of clearing, but they have been suppressed by signals from the cancer. In the lab the cells are selected and bred so that you have a pool of hyped-up cytotoxic T cells, which when transfused back into the patient are so aggressive even the suppressive signals from the cancer don't stop the killing.
In fact, it's the mutations in the cancer which allow this therapy to work. Mutations are what makes the cancer 'non-self' - the more they have, the more attention they get from the immune system. If they try to hide their mutations (all cells must present the products of their DNA on the cell surface), they get removed by natural killer cells (so called because they naturally kill cells unless they display what they are meant to on the cell surface).
The article actually talks about another type of treatment called CAR-T cell therapy. This is a bit different. What you do in this case is you take a T cell from the patient (not a tumour-infiltrating T cell - instead you want an effective T-killer cell), and they graft an antibody which is specific* for the tumour onto the cell. There are a few other steps to make sure that the cell survives in the patient, but essentially when you infuse this cell (ok they give more than one) into the patient, it recognises the target (hopefully the tumour), divides and kills, divides and kills etc etc until the tumour is gone. Then hopefully it stops dividing, or you end up with a T cell tumour.
In this case - your question is right on target. The cancer can and does mutate to avoid this therapy. In this particular case the antibody is for CD19/CD20 (I can't remember), and it was able to clear the tumour before it could evolve to drop CD19/20 from the cell surface. In other patients subsequently treated, a proportion of them have relapse with tumour cells not displaying CD19 on the surface.
In fact, this is the achille's heal of CAR-T cell treatment. It is essentially a very powerful antibody, but for it to work it needs a few things - 1. The tumour must have the target marker on all of its cells - i.e. it can't evolve out, 2. You must be happy to lose any healthy cells which also have this marker.
In this case the patient lost all of his B cells. This is a powerful component of the immune system, but actually, you can get away without it, thankfully. This treatment wouldn't work for a T cell leukaemia/lymphoma. Removing all of your T cells gives you AIDS, which is no better than having a terminal cancer (when it's not caused by HIV, that is).
I just want to say that you have a fantastic way of writing that explains these therapies extremely well. I've learned about these therapies in class, but your explanations felt even more fluid.
Just a clarifying note: mutations and foreign proteins are not always responsible for the effectiveness of TILs in all cases. For instance, in a report from this year, patients with HPV (Human Papilloma Virus) positive cervical cancer were treated with TILs. It was expected that most of the TILs would be directed to HPV antigens or mutated protein (neo-antigens) because both would be maximally foreign to the immune system. However, it was determined that T cells against the wild-type protein CT83 (also known as KK-LC-1; which is a wild-type cancer associated antigen) dominated the response in at least one patient.
Thanks for that - I'll have to have a look at that when I get back on my network.
As you say, there are many reasons why cancer isn't self - neo-antigens are just a facet of that. Are cancer associated antigens the same thing as cancer-testis antigens? To be honest, I've never really groked CTAGs - they don't make sense to me. Why does the thymus not expose T cells to them? Why does cancer produce them? To many questions..!
Can this treatment be designed to target the mutations? ( So you didn't lose healthy cells ) I'm assuming the mutations present on the cell surface as well, but I am unsure.
In that case, would any cell that mutated to avoid there treatment, de-cancer itself?
That would be a sort-of holy grail of cancer therapy. The problem is that the best equipment to develop a high-affinity antibody, or find the correct T cell receptor to the mutation is the patient's immune system - and they've already done it.
Predicting what sort of antibody or T cell receptor will bind a specific mutation (more technically a piece of protein with the mutation in it - about 10 amino acids long) is hugely difficult - it requires a very good understanding of how all the amino acids fold and interact in a 3D spatial model, and we simply aren't there yet.
Your last question really depends on the mutations. Further mutations would stimulate more of an immune response, but a mutation could, for example, increase the ways a tumour cell hides from the immune system. On the other hand, it would be hard for the tumour cells to de-mutate itself to avoid TILs already specific for that mutation.
>I chose this trial because the I liked the fact that my own immune system was being boosted to fight my cancer.
I work in biotech and a very successful CEO of mine once told me "When I'm evaluating new (bio)technologies, always bet on tech that replicates/take advantage of a currently working biological system. Tech where everything is synthetic/relies on a custom designed system/etc is much more likely to not work in the long run."
Re: The IL-2 infusions being hellish, I can guess why that would be (pain, fever, delirium, and so on), but I'd be interested in a first-hand account from someone like you, who seems to be so able to communicate these experiences. In short, what was the hellish part of it?
You've listed the main side effects of the treatment: pain, fever, and delirium.
About 20-30 minutes after receiving a dose of IL-2 by infusion, my body would undergo violent bed-shaking rigors for 10-20 minutes. I had the worst chills I've ever had, followed by breaking out in a hot sweat when it had passed. This was very unpleasant.
After each successive dose, the effects would worsen.
Essentially, the doctors were trying to take my body to the brink of experiencing a cytokine storm (https://en.wikipedia.org/wiki/Cytokine_storm) to jump-start my immune system.
This was a pretty miserable part of the treatment, but (in the end) obviously worth it.
The research doctors at NIH have been refining treatments with IL-2 for almost two decades for thousands of patients. They've gotten enough experience to recognize and mitigate the issues that may develop.
In my specific case, they weee concerned that I might have a heart issue that was unknown (I don't). For the sake of my own safety, I was given the treatment in ICU. For most patients, this is unneeded.
Actually, my biggest risk was contracting a superbug with my severely weakened immune system. The last NIH patient who died from the superbug was a few rooms away in ICU at the NIH Clinical Center at the same time as me. (I knew the doctors were taking extra precautions with me, but I was totally unaware of was what happening down the hall from me.)
When I used to work in a lab, these types of reports were common and delightful to hear, but very few patients were as well informed and granular with their understanding as you are.
I just lost my mother to cancer and it was a hellish experience. It gives me joy to know someone out there beat it and that people in the near future may have a better chance than mom did. Congratulations on the recovery. Wish you many wonderful years full of life!
I might be doing this treatment at some point since I failed Ipi and PD-1. -- What were the long-term side effects for you? -- Have you had neurological/memory problems since?
My biggest side effect has been vitiligo, the loss of color in my skin. The treatment caused my immune system to attack my melanocytes in addition to my melanoma cells. This is actually a great prognostic indicator.
If that's the worst of it, I can handle it, especially considering the alternative.
Nope. As far as I know, I've retained my immunities.
However, I do know that my seasonal allergies have changed slightly since treatment–they've actually moderated. I don't know if that's due to the treatment or just an age-related occurrence.
Cutting edge scientific research is expensive. I don't know why people expect advanced medicine to be cheap. Synthesizing or extracting complex proteins, using rare medical radioisotopes, medical scanners based on the most cutting edge engineering and physics... Almost no endeavor besides physics and medicine makes regular use of superconductors, antimatter (for PET scans), etc.
> I don't know why people expect advanced medicine to be cheap
Nobody said cheap. People (me included) actually expect immunotherapy to be expensive. A course of Perjeta/Herceptin can go to $188k (per [1]). But many are already outraged by this number. A course of Rituxan can be about $14k to the patient, and you could say it's dirt cheap compared to Herceptin, but it appears the cost to the manufacturer is $300 ([2]).
As for superconductors, antimatter, and all other sci-fi sounding things, the cost of an PET scan is about $7k, and of an MRI scan is less than half that, so that can't explain the million we're talking about here.
I think we simply became insensitive to hearing big numbers in the context of healthcare. The birth of my second son cost my insurance about $130k (they covered 90%, but I still had to fork out about $15k), and he didn't have any surgery, or anything major. So yes, I can understand $1MM for cancer treatment, but allow me to be mindblown all the same. I don't think $130k was reasonable for a delivery, and I don't think $1MM is reasonable for immunotherapy (which again, does not involve surgery).
I'm going to assume the lion's share of costs in something as routine as a regular delivery of a baby (i.e. no complications) is probably going to be: Hospital expenses and doctor/surgery costs. IMO paying thousands of dollars to surgeons is definitely justified. I have several doctors in the extended fam, some of whom are surgeons. One of my cousins is studying to be one. Its just fucking crazy how much effort is required to be a doctor (not to mention all the costs assosciated with the education itself). So personally, I think the labor costs of surgery are justified.
The hospital charges make sense too as you're under supervision by trained nurses and living in a room built with specialized equipment.
I had an appendectomy recently. Everything included (surgery, hospital charges, drugs etc.) came to ~ $55k. Insurance paid most of it and I was ultimately charged around $5k. With that in mind $130k doesn't sound unreasonable for a delivery of a baby.
> $130k doesn't sound unreasonable for a delivery of a baby
While I'm accustomed to hearing this kind of thing from the USA, know that for citizens of any other developed country, that is an absolutely absurd amount, to the tune of 10x or 20x the proper cost.
I've recently had friends in both Japan and Australia, hardly countries with poor healthcare, give birth and in both cases the cost was around USD$5k. That's private, by the way - public would have been free (ie covered by the system paid for by the 2% medicare levy in the case of Australia).
I don't disagree the costs of heathcare are super inflated. My contention (and this is purely anecdotal, I don't have hard facts) is that healthcare workers in the US get compensated extremely well. I would like a comparison of doctor/surgeon compensation in different countries... I believe US healthcare professionals get compensated very well in comparison to those in other countries.
These numbers [1] are old but are probably still in the ballpark. US healthcare workers are compensated well, but not all that much more than comparable developed countries. And quality of healthcare in the US is top ten at best [2].
No, the prices are only explainable by profound inefficiency and corporate rent-seeking. The US is paying hugely inflated prices for (at best) similar outcomes to its peers - now that's market failure!
Needless to say I expect the US will adopt a single payer healthcare system within the next 10-20 years, like every single one of its peers, simply because the current system is unsustainable.
Even only taking salaries into account, you've got the surgeons and all associated staff in the removal of the tumour. The guys in the lab to cultivate the white blood cells, everyone who needs to fill out paperwork, more surgery, monitoring and check ups.
Then add into that all the costs of running a hospital, proprietary medication, regulatory compliance, cost of all the single disposables.
The costs very quickly add up to a few hundred thousand before anyone's even taken a profit.
I presume the incremental cost of treating each additional patient will be considerably smaller once the overheads of treating the first person are made.
Not necessarily. Even in regular use, this treatment will still involve killing off the patient's immune system, which will require days in hospital isolation. In addition, the culturing and screening of the immune cells to create a population that is primed to fight cancer is a labor-intensive process that has to be done for every patient.
Small question: How do you get into a trial like this? Did someone choose you? Are trials like this announced somewhere and you did apply? Word-of-mouth? Someone related who works in this field?
It's hard to imagine how it feels to be diagnosed with cancer but I guess in many cases, if the outlook looks dim, a trial like this would make the most sense? Or not?
Getting into a trial usually involves a lot of criteria that the patient has to fulfill (age, subtype and stage of the disease, results of various tests, all kinds of other treatments not working, mutations or lack of them, good performance status, good organ function). If the patient fulfills them their doctor just asks them.
This research and your story give me so much hope for people who have inoperable cancers and can't handle chemo. I look forward to the day that we can rank cancer among syphilis, tetanus, and all of the other past disease scourges of man made completely eliminable by a non lifelong treatment.
My melanoma was initially an ugly black mole that grew on the side of my face, which I had removed by my dermatologist and sent to pathology for analysis, where it was determined to be a melanoma of intermediate depth.
Because of its depth into the skin tissue, I had a wide excision (where more skin tissue is removed) and a sentinel lymph node biopsy which removed four lymph nodes that were most closely connected to the tissue that was removed. Of the four nodes removed, three were negative (clear) and one had a micro metastasis (micromet) sized 0.18mm. This placed me at Stage IIIa.
The melanoma developed as tumors in my lung just over a year later, putting me at Stage IV.
The primary symptom I had was the mole. I felt completely normal.
As far as the treatment, read my answer about the "hellish" nature of it in another reply.
Thanks for the info. This is one of the most terrifying cancers imo, metastating so fast, and with so few symptoms in the beginning. Congrats on your recovery !
Woah. That is seriously cool, that we can do that. Congratulations on your recovery, and thanks for going through that for science.
Can you maybe elaborate a little on how they selected the cells to lab-grow? Step 2 and 3, in particular. By what criteria did they divide them between petri dishes and how did they test how efficient they were at destroying cancer cells? (Did they feed them parts of your tumor or something?)
Chimeric Antigen Receptors are an impressive first step into designed biological technologies. There are new challenges associated with their design and deployment - but there are also a lot of theoretical capabilities that are unmatched non-protein therapeutics. It's very much a new paradigm in treatment. These are 'cures' to human misregulations very much like how small molecules 'cured' patients of foreign diseases a century ago (and do not cure patients of regulatory diseases).
If you want to build your own chimeric antigen receptors we've built a digital infrastructure to allow you [1]. Though we just made public our generic protein design software (thanks ShowHN! [2]), we're employing the same underlying digital infrastructure to build, evaluate, and manage CAR designs in high throughput [3]. The drug approved here was painstakingly designed by hand [4], while we think the technology now exists to permit many more such advances to be created at a much more rapid pace.
Wow, this seems really amazing. I read some background from your show HN, but does your software mostly make DNA plasmids? How would you go about integrating that into a eukaryote? I think in the article they used a retrovirus. Also, plasmids have a maximum size for proteins, do you have a vector to incorporate larger proteins?
The software 'compiles' down to DNA - which can be produced and delivered in any form useful to clients. Most of the time that deliverable is a plasmid.
The plasmid DNA is then used as a reagent to manufacture the physical retroviruses that are used to transduce the extracted T-cells which are then reimplanted into a patient.
Practically, multiple plasmids, each containing a single component of a synthetic retrovirus are given to 'viral manufacturing cells', and the output is pool of virus that is infectious only once, and has DNA that encodes the CAR design as its payload. That virus is then given to the extracted T-cells, where it infects them with the viral payload and integrates its genetic payload into their genomes. Once integrated, the cells are tested to ensure they are not further infectious, then reimplated - newly 'upgraded' with DNA that encodes a synthetic CAR protein that is now capable of homing in and killing the target cancer.
Getting all that payload into a plasmid is certainly an art. A lentiviral capsid has a physical pressure capacity such that it can hold <13kb of DNA. This is precisely why it's so important to have good ways of testing/pruning/evaluating new protein designs so that you can prune down a theoretical design into precisely the minimal design required for effect.
Thanks for this highly informative answer. I'm particularly interested in vaccine-based cancer immunotherapy. Do you know of any good survey papers covering that?
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.
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.
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.
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.
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 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.
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.
That kind of comment isn't OK here. Michele is sincere in her commitment to learning whatever a layperson can reasonably learn about medical science, and sharing what she's learned with generosity and humility.
There's nothing stopping you from asking Michele to expand on her position, and it would be great for you to educate her if you know things that she doesn't. But on HN, personally cruel comments are off limits.
Equally sadly, a brand spanking new account (created minutes ago and this its first comment) with a doctor-y title gives you even less credibility than I have and looks like trolling. Just an FYI.
I apologize for the way the parent comment replied to you. I do have some questions though.
What is it about the therapy that is Frankenstein? Frankenstein implies the haphazard and artificial sewing of parts. However, every drug or treatment we use today is artificial, a.k.a. created by humans, and by reading the article, the development of the immunotherapy was far from haphazard. Furthermore, you mention elegance and a light touch. How can those terms be defined in a clinical setting? Is elegance defined only by your opinion? What is elegant to one may not be to another.
Lastly, I would like to agree that if possible, a light touch is always valued over a heavy one if the outcomes are the same. But in this situation we are in today with cancer, there is no room for valuing such pleasantries when lives continue to be at stake. Most would want the survival of their loved ones if a heavier touch must be used. In fact, this immunotherapy is indeed the lighter touch compared to extensive chemotherapies.
What is it about the therapy that is Frankenstein?
The principle of BIG ZAP followed by pronouncement that IT LIVES! We like this kind of drama. It makes it easy to claim credit for the outcome. Subtler approaches get a whole lot more "correlation does not prove causation" type feedback. But it sort of overlooks the fact that the body is the battlefield and if you have a scorched earth policy towards the disease, the remaining shelled out husk may not support life.
Lastly, I would like to agree that if possible, a light touch is always valued over a heavy one if the outcomes are the same.
In my experience, the outcomes are not the same: A lighter touch gets superior results because it does not leave one with a shelled out husk that cannot support life.
Without going on at length, the TLDR of what my mother did for my father was she focused on keeping him hydrated and adequately nourished. He lost a third of his body weight prior to finally being diagnosed with colon cancer. At a time during his treatment that most colon cancer patients are losing weight, he was gaining weight so rapidly that his doctor yelled at my mother to slow it down. My father had a longstanding heart condition and the doctor was concerned that the sudden weight gain would be too much strain for his heart.
I have followed some similar principles in recovering from my incurable health issues. My condition involves significant gut impairment, so much so that CF medical teams routinely include a dietician. Yet, the last time I checked, the state of the art was to encourage CF patients to feast on junk food because CF patients are encouraged to eat a high fat, high salt, high calorie diet. I never counted calories. I did work on getting enough fats and salt, but a higher priority for me was to eat nutritionally dense foods and high quality foods. I did a fair amount of research (or took advice from other people who had done so) and I got very picky about the kind of salt and fats I would eat, as well as the kind of food. This has yielded good results and allowed me to get off a long list of drugs and other treatments. I am gradually getting my life back when the norm for CF patients is steady deterioration until they finally die, often at very young ages.
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).
Why can't we focus a lot of funding on this project? This is exactly the kind of thing for Government to lead rather than wasting time trying to healthcare out.
Most people don't seem to realize the kind of progress that's been made in recent years with CRISPR etc. These problems are becoming data problems rather than biology/chemistry problems. The public (government) should certainly be funding many teams with small amounts of money ($10,000 to $100,000 say) rather than pouring billions/trillions of dollars into "proven winners" (big pharma) that mainly come up with therapies rather than doing basic research.
Honestly I think the same argument applies to so many areas of the economy: alternative energy, space travel, growing food, and so on. We could be finding so many "cures" for relatively modest investments that our current system has actually become very expensive due to the opportunity cost of not doing so. I've spent most of my life asking what we are all working for and towards but have come to the conclusion that keeping everyone busy is the goal now, not progress.
This could discourage smaller companies from picking it up (ex. to build upon it, from which in the long run everyone will profit, see open-source) and make CRISPR-based treatments more expensive / unavailable (ex. large companies owning the patents artificially inflating the price, may be even more than the old technology it replaces).
I do agree with what you're saying but don't downplay the healthcare talks either :/
I lost my health insurance, again, to Obamacare. But it doesn't matter because no one in my state (ks) is willing to sell individual health insurance next year... I think there are three states headed this way last time I read.
So yes, the repeal of Obamacare does need to happen sadly :/ I'm hoping for a partisan solution, but at the moment members of Congress are busy promoting their political parties instead of working together.
Oh wow. The main stream media doesn't even report this problem with Obamacare. Is there a national health exchange that you can buy your insurance from?
How many of you or people you know would run away from new treatment trials ? I've been surprised to see a few people getting more than annoyed at suggesting it. "I'm not a guinea pig" was the recurrent answer.
If you have no options left, I suppose it's the only sensible thing to do. Either you're 100% sure you die from cancer, or you take an unknown chance that might save you.
Then again, not all people are very capable of rational thought.
The manga Hellsing features a character named Alucard who is no relation to the Castlevania Alucard. This Alucard is, in fact, Dracula himself, who was defeated by Abraham van Helsing and, rather than accept destruction, swore to be a servant of the van Helsing family, who employ him as a powerful weapon against the undead.
I mention this because it seems HIV is the Alucard of immunological treatments: a terrifying incurable disease which we now use as a potent weapon to fight other diseases. The thing that made it so terrifying -- its tendency to attack immune cells -- also makes it incredibly fit to purpose.
If we can design CARs for cancer specific markers or have the technology to create other immunotherapies, I don't see why we couldn't do the same for any antigen including antibiotic resistant bacteria. A quick search shows that there is some work in this area already.
Agreed. Cancer is random and having a genetic likelihood of a treatment-resistant cancer reduces the chance of that sequence spreading. Unlike cancer, bacteria and viruses mutate as they move through the population and slowly become resistant to everything we throw at them. Being treatment resistant is a help, not a hinderance to their genetic propagation.
With growing global density and antibiotic abuse, it's the things like MRSA and syphilis that are likely to never disappear.
I'd love to see a comparison done on the news pieces we're reading today about CAR-T and compare it to the news stories a century ago as penicillin was discovered and began being used as a treatment.
Everyone is afraid to over-hype this, but take a moment and consider that we're now re-wiring the human immune system to fight things it previously couldn't. That's incredible.
They mention in the article that the skin cancer appeared to be a metastasis from his bones. I expect that all of these cancers stemmed from a single source in his bone marrow.
In essence, the tumor infiltrating lymphocytes (TIL) adoptive cell therapy was as follows:
1. The doctors removed a melanoma tumor that was growing in my neck.
2. In the lab, white blood T cells (T lymphocytes) that were attempting to attack the cancerous tissue in my tumor were isolated into at least five different petri dishes. The white blood cells' growth was stimulated using IL-2.
3. Those samples that grew the most and attacked the cancerous tissue (2 of the samples, in my case) were then expanded to a total of 130 billion lymphocytes in the lab.
4. I returned to NIH for a week of immune system preparation, specifically the almost complete suppression of my own active immune system using harsh chemotherapy. This was to allow my body to accept the new lab-grown immune system.
5. Once my immune system was sufficiently suppressed, I received all 130 billions of the lab-grown lymphocytes. The immune system was then stimulated by having five large doses of IL-2 every eight hours over a two day period. (Note: This was hellish.)
6. After a week or so, my immune system had recovered and I was released from the NIH Clinical Center to return home. I was given an anti-biotic to take for 4 to 6 months to reduce the possibility of contracting a specific pneumonia (PCP).
7. I returned to NIH monthly for scans monthly for the first three months. After month one, my tumors had shrunk 33%. After month two, 66%. After month three, they were almost complete gone. My immune systems had essentially been immunized against some of the mutations contained in my cancerous melanoma cells.
8. I was declared NED (no evidence of disease after 15 months) and a complete responder to the treatment after 21 months.
Now, almost five years post-treatment, I have had CT scans and brain MRIs every six months with still no signs of melanoma. My doctors have told me that I'm likely cured.
Immunotherapy works. I chose this trial because the I liked the fact that my own immune system was being boosted to fight my cancer.
Further info: https://en.wikipedia.org/wiki/Tumor-infiltrating_lymphocytes
My doctor is Dr. Steven Rosenberg of the National Cancer Institute.