Cancer ‘vaccine’ eliminates tumors in mice
med.stanford.edu
med.stanford.edu
Three weeks ago she had a radical hysterectomy and partial lymphadenectomy to treat stage IIIc ovarian cancer, and we’re back to try to aid her in her recovery to prepare for chemotherapy. Chemo should start next week, but we are hoping to also participate in a clinical trial for atezolizumab. This is a drug that essentially blocks the cancer cell’s immunosuppressive mechanism (expression of PD-L1) and allows the body’s natural immune response to do work on the disease.
Suddenly inspired to learn more of the nitty gritty around how cancer and the associated therapies work, I’m shocked at how sophisticated the battle is. At least in this case, the unregulated reproduction of cells is just the beginning, and my lay mind can’t grasp how simple mutation is responsible for it. If someone told me cancer was sentient with a will to thrive, I’m now much less inclined to laugh them off.
Therapies that arm our own immune syatem in the fight against this monster really seem like the light at the end of the long, dark tunnel.
I hope your morale is as high as possible, faith and energy are useful to help your loved ones heal in order to endure side effects of treatments. Also it seems immunotherapies are often well supported by patients across the board, so hopefully it will be easier to fight.
The author concludes the autoimmune system is key to beating cancer.
Be strong, be lucky and hang in there.
As a non-medically trained support member I have gotten pretty good in talking with the doctors about my family members cancers. I help explain them to others in my family and when I sit in the conversations with the doctors I stop them talking to make sure the patient is taking it in and understanding. I have unfortunately worked with many doctors and I have never had a negative experience with one when I stop them and ask the patient do you under stand and have them repeat what they heard. I even did this with my son when he was 8 because it was his body. I would than have a notebook and have them write down their questions throughout the day for when the doctors showed up (Usually around 6 or 7 AM)
I encourage everyone that enters the cancer world, as either a parent, spouse or close friend, to learn everything they can. The more you learn the madder I get at cancer research and specifically about pediatric cancer research. There is a Radio Lab Podcast and it got pretty intense for me to listen but I also understood cancer at a much better concise way after listening to this and specifically how cancer spreads. http://www.radiolab.org/story/91714-devil-tumors/
Three piece of information I always give to everyone:
1) The most important staff member of any doctor or surgeon is the Nurse Practitioner. They are the Master Sargent of that practice. Get their contact information and always make sure they are informed of what is happening.
2) Never assume that the different doctors are communicating, because 90% of the time they don't. Not between the surgeon and oncologist and even residents to other residents. Always ask question to make sure they know what is happening to you. Your the one making sure the different silos are talking.
3) Have two people you can call if you have any concerns. You get a gut feeling you don't ignore it. Doctors miss things all the time and you call that person that you trust. My mom started coughing after surgery and I knew it was serious. Two doctors from the surgeon's team show up and basically don't think it is serious. In the room I calmly said that we both have concerns and think someone else needs to see this. They were figuring out someone else to come to look at her. In the mean time I walked out of the room and called the surgeons nurse practitioner directly and state that I thought my mom's vocal cords were paralyzed, which I already ask the two doctors if they thought that was the issue. We were in the ICU within 10 minutes after that call and we were there for 4 days. My mom's voice came back 2 weeks later, she is a license counselor and her voice is her job. The thing is have a plan on who you can call if you get scared about something.
My question is: if we boost the immune system, what are the side effects? Is an immune system that's compromised (e.g., loses battle with cancer) indicative of other problems? In other words, in a way, is cancer actually a symptom?
Good luck. And God's speed.
Fuck cancer.
A cancer needs a good blood supply to provide itself
with food and oxygen and to remove waste products. When
it has reached 1 to 2mm across, a tumour needs to grow
its own blood vessels in order to continue to get
bigger.
Some cancer cells make a protein called vascular
endothelial growth factor (VEGF). The VEGF protein
attaches to receptors on cells that line the walls of
blood vessels within the tumour. The cells are called
endothelial cells. *This triggers the blood vessels to
grow so the cancer can then grow.*
OK, what about this trial...atezzolblablblah.. What's it do?
Programmed cell death protein 1 is a cell surface
receptor that plays an important role in down-
regulating the immune system and promoting self
tolerance by suppressing T cell inflammatory activity.
PD-1 is an immune checkpoint and guards against
autoimmunity through a dual mechanism of promoting
programmed cell death in T-cells in lymph nodes while
simultaneously reducing cell death in regulatory T
cells.
...
PD-L1, the ligand for PD1, is highly expressed in
several cancers *and hence the role of PD1 in cancer
immune evasion is well established*.
This thing isn't just some dumb pathogen floating around that just DoSes your body. It's digging tunnels and cutting phone lines. It has strategy.
See also epithelial to mesenchymal (ETM) transition, in which cells lose their anchors and become an entirely different kind of cell so that it can better infiltrate other parts of the body.
It's pernicious and highly specialized because that's why it survives. And that's why everyone will die of cancer if something else doesn't kill you first.
EDIT: OK I've done some reading about cancer and evolution. Clearly there is an evolutionary process happening inside each person's body that "selects" for cancers that are good at their "job". However even the most successful of those have no hope of passing beyond their host unless they also mutate a transmission mechanism for themselves, which happens much less often (but the Internet tells me it has been known to happen in dogs).
Oncoviruses are another transmission vector. HPV, or human papillomavirus, is a virus that causes warts (of all kinds) in humans, and also causes several kinds of cancer, including cervical and esophageal cancers.
A third way would be a pretty rare thing in humans, but is thought to be behind some of the canine cancers you mentioned: direct transplantation of cells. The tasmanian devil is on the edge of extinction thanks to a facial cancer they get from each other through this mechanism.
Generally, infectious cancer is a result from a population that either regularly has open wound contact, and or is very closely related genetically.
Given enough time cancer can even start to survive on it's own: https://en.wikipedia.org/wiki/HeLa It's actually become somewhat difficult to avoid cross contaminating samples with this cell line.
Cancer cells simply lack the trigger to stop growing.
The cancers that haven't mutated to emit VEGF don't survive to grow and kill you.
It's natural selection, not intelligence.
esp. in combination with studies r intermittent fasts/food in general. Neven Orhel's (fiction) books are also in the line with intermittent extremes / how healthy cells can cope with them and cancer cells can not, which is well in-line with the finish saying(was something like "if sauna doesnt cure you no doctor will" - pls correct me here)
+1, Fuck cancer.
I'm crying, my Mom passed away almost 3 years ago, but that sentence got me. Godspeed to the Scientists and best of luck OP's wife.
Your comment made me cry.
"Squeeze her hand for a stranger."
OP, I will keep your wife in my thoughts.
https://today.uconn.edu/school-stories/recruitment-begins-wo...
I hope it works as well for her.
and very importantly for you and your wife, many of us consider the PD-1 therapies as the biggest battles and biggest victories that we've ever won against cancer. it is extremely difficult to overstate how powerful the anti-PD-1/L1 biologics are.
and it's also extremely hard to overstate how much research scientists in the field live and breathe and toil to harness nature. you have a care staff of perhaps a dozen at the hospital, but just remember that there are tens of thousands of people working day and night to find better therapies and cures.
nature is always throwing us curveballs, and in the words of rich feynman, "she's never gonna let us relax." but we'll figure it out, and win. in the meantime, that clinical trial you mentioned is investigating the true power of our biggest achievement to date.
it isn't ethical to push your wife into the trial, so i'll just say this: if i had serious cancer, i'd find more than one anti-PD-1/L1 trial to try to enroll in simultaneously. that way if i got excluded from one because i didn't meet the criteria, i have a next step in hand without thinking about it any more. if by chance i got into more than one, i'd withdraw from the others (obviously). just my two cents.
good luck.
Incidentally, at least for my mother, the injections she would get shortly after her chemo treatments -- if I remember right these were referred to as "white cell-count booster shots" although I don't remember their actual medical terminology -- these left her feeling far worse than the actual chemotherapy. It most affected her appetite, namely she didn't have one for 3-4 days after getting the injections. We tried everything the doctors and nurses recommended, and a few that the internet recommended [don't do this, but we were desperate], all to no avail. Finally, I talked her into smoking a joint -- and this woman never drank anything other than communion wine or did any drugs in her 55+ years of life before this. Appetite problem solved. It was back in spades, almost like never before. I guess what I'm saying is, if your wife finds herself with the same issues [and I hope she does not] never mind the 'stigma' associated with it -- weed works.
Very best of luck to you and your wife.
For adjuvant therapies for cancer, I highly recommend looking into sulforaphane.
Dr. Rhonda Patrick has a tremendous corpus of scientific research and plenty of anecdata on the internet about how it is helpful and has helped others with cancer.
Hang in there, and don't forget to take care of yourself too. Being in the role of caregiver is fucking exhausting at times. If you're like me, it falls to us to be the shield against well-meaning but poorly informed acquaintances shilling this herbal remedy or that metabolic supplement or this fantastic ketogenic diet backed by the research of some doctor nobody's heard of because Big Pharma... Just nod and smile and say you'll look into that and give them the middle finger in your minds eye. Try and find some support system, whether its a caregivers group or friends who have been through it, or even friends who haven't that you can still vent to. There's a lot coming at you, and more to come. Its ok to take some time for yourself some too.
Best wishes, man—I'll be thinking about your family.
Each family's experience is unique and I can't begin to imagine what it's like to fight the sickness for years.
My heart goes out to the OP's family, and anyone else with an unforgiving disease. I am not a religious man, but I wish your wife the best of luck in her recovery.
I knew cancer was bad and had a lot of research surrounding it, but I was blown away by the uncertainty for patients and the incredible amount of resources put into solving/treating the disease and supporting the people going through it. After immunization, chemotherapy is probably the most important medical discovery in human history. If immunotherapy can carry us past that, how amazing!
The immunosuppressive therapies are new since we went through treatment and I’m hopeful. If or when we have to fight again, we’ll have new weapons, I’m optimistic.
I hope you find strength, comfort, and support enough to be a support for your wife. Others have gone through it, empathize, and are rooting for you. Fuck cancer.
I hope this translates well to humans and other mammals.
On this topic when I was an academic a few years ago I had one of my undergraduate student project groups go through an entire year of Cancer Research (one of the highest ranked cancer journals) from 10 years previously and have them find out what happened to the work published. Rather depressingly the vast majority went nowhere and when my students contacted the PIs to find out why most of the time it was for totally non-scientific reasons like the group lost funding or someone left.
This isn't mutually exclusive to the treatment being in the public domain.
Of course if you wanted to you could make this treatment yourself - it is not that complex.
For every therapeutic target there are many chemical/biological solutions that can work. If an off-patent compound shows some effect in a pathway, a patentable variant can usually be made.
But to address your specific question, generics are drugs that come onto the market all of the time without patent protection.
well... you can write a patent that is so obfuscated that the public cannot learn from it...
In such case the patent office should reject your patent claim as patent laws usually require that the description of the invention being patented should be understandable to professionals of relevant domain, who should be able to replicate it based solely on that description.
While this does happen, and sometimes things obvious to a practitioner get patented, obfuscated patents are contrary to the purpose of patenting.
Also by definition a patent is in the pubic domain (for knowledge) and the publication is of course a public disclosure.
Also for clarity (and responding to the concerns of the original questioner) it's highly unlikely that this combination will be patented by anyone - this isn't how patents are used in drug development. Anyone with access to the necessary drugs would --in theory-- be free to open a clinical trial to test this approach.
This type of research tends to be publicly funded. However, that doesn't prevent it from being privately patented because of the https://en.wikipedia.org/wiki/Bayh-Dole_Act
According to the paper, these were the two drugs used:
* "CpG SD-101 was provided by Dynavax Technologies"
* "Fc-silent Anti-OX40 (CD134) mAb was purchased from Absolute Antibody"
SD-101 is already in clinical trials. http://www.dynavax.com/our-pipeline/cancer-immunotherapy/sd1... The anti-OX40 was a laboratory antibody, presumably as this was for a study in mice. However, there are various anti-OX-40 molecules in clinical trials, which could be used.
To get clinical trials going with this approach isn't a matter of patents - it's a matter of one or two companies (depending on ownership of suitable molecules) deciding its something they want to do, and then doing it. My guess is that Dynavax will already be exploring this.
What I wonder is why this is being discovered only now.
Curing cancer with a bullet works too but the host suffers some adverse side effects.
but immunotherapies don't kill most people, thankfully. there are also many ways that you could assay the patient to see how they might react to immunotherapy, but i dont know whether these are done clinically or not.
"Treatment" does not convey accurately the strength of this approach.What's the chance of this developing into a regular treatment for most types of cancers, within, say, the next ten years?
immunotherapies don't work for 100% of people or 100% of cancers, and some cancers seem to grow resistant to some immunotherapies after multiple rounds of treatment.
there are a lot of limitations and strengths of immunotherapies that we don't even have a clue about yet-- by my totally made up estimation we have about 10% of the puzzle figured out, an additional 30% which we have partial or incorrect understandings of (but at least we realize it and are working to clarify things), and 60% remains unknown unknowns.
but remember: we don't need to understand quantum gravity or have much knowledge of how gravity works whatsoever to make an airplane that defies gravity at our will. it's the same way with immunotherapies, except replace "gravity" with "cancer." we can do an awful lot with what we know.
immunotherapies are incredible-- literally the data is often unbelievable at first glance.
For people outside this field of work like me (a software / cleantech guy), is there a concise spreadsheet to show the state-of-the-art?
i.e. Listing different types of cancers with the most promising immunotherapy treatments for each type, expected confidence and success rates, trials that one can enroll into?
It'd be a good first place to go to whenever we hear of someone who has 'cancer' - that word is so generic that it's hard to figure out what our action item should be.
doubtful imo. the state of the art is rapidly changing, and plenty of things are happening behind closed doors.
clinicaltrials.gov is your best bet but the expected success rates is not something anyone would willingly have as public information.
Many of the cancer immunotherapies I've heard about are systemic and risk overengaging a diffuse immune response against multiple tissues. This approach trains in-situ using strong signatures from individual tumors first, before the antigens spread out across the body. Perhaps this localizes the cancer antigen signature better, so antibodies cause less collateral damage?
But CAR-T therapy should do something similar, though re-introduction of the antibodies is systemic (untargeted). Is the administration of this therapy directly into the tumor somehow essential to its specificity?
Generally I view these press releases with a skeptical eye, as the researchers have a need to "talk up" their work in order to keep the funding coming in.
On the other hand, Irving Weissman and the labs at Stanford are well respected and not known for spurious claims - often though, the problem with these therapies isn't so much potency as it is persistence, with recurrences being relatively common longer term (and many therapies simply don't translate from mice to humans well).
I'd be interested in having someone with in-depth knowledge of this field explain how the OX40 receptor work here differs from the CD47 work also being carried out at Stanford (besides being a different target protein), and existing CAR T therapies being tested elsewhere - although certainly this seems very encouraging in any case.
The animal immune system has evolved over hundreds of millions of years to target and destroy pathogens. Why use an indiscriminate chemical treatment to destroy cancer when our body already has a self defense system that operates with pinpoint accuracy, unparalleled target recognition capabilities, and ubiquity throughout the body. All these things make it a terrific candidate to destroy cancer.
Using it just makes so much sense.
This isn't always true. You body can start attacking itself if cells start misidentifying one another. This can lead to Lupis, MS, Ruhtomotide Arthritis and various other auto-immune diseases.
I'm thinking of (1) lower but high enough numbers of normal cells somewhere between the cancer cells, and (2) plain accidents like the needle pushed too far / not far enough.
It's not just a preventative measure to eliminate the potential of possible cancers from emerging. The cancers the mice already have goes away.
[0]: https://www.reddit.com/r/Futurology/comments/6xsokg/duke_uni...
Relatively new T-Cell therapies "train" the body's own immune system to recognize and delete cancer cells with much fewer negative effects than traditional treatments like radiation or chemotherapy.
Stories like this don't mean an end to cancer, but it's still very good news.
Immuno-Oncology is the hot new shit, a huge wave of biotech startups is betting everything on it.
Celgene bought Juno for 11bn recently, Gilead bought Kite for 12bn.
Puts tech startups into perspective :) Tres commas...
Isn't there a fast-track for experimental treatments for late stage cancer?
Personally? It had better be an airtight law accounting for the edge cases that could allow certain populations to be taken advantage of. For example, if anyone with a terminal illness can try an experimental drug, could a pharmaceutical company charge for said treatment? Or use the data from trying this treatment on the patient to further their own research?
I guess it just doesn't sit well with me since researchers in the US have had a history of taking advantage of certain populations in furthering progress (Tuskeegee, prison populations, mental institutions).
What would be the problem with it, provided that the treatment is given for free and the patient has no other options?
Medicine and medical research goes slowly and cautiously because we wish to protect people. To end this comment, I wish to go back to my statement that if this country goes in the direction of right to try, I sincerely hope lawmakers ensure protection of the patients that could benefit.
For breakthroughs, 10 years before widespread availability would be a maximum. In late stage cancer, especially where options for treatment are few, rollout could be very fast, like 2-5 years.
2) The pathway from first-in-man to approval can be a lot shorter than 10 years for promising drugs or combinations. Pembrolizumab, for example, took roughly four years: https://en.wikipedia.org/wiki/Pembrolizumab#History
"Eradication of spontaneous malignancy by local immunotherapy" http://stm.sciencemag.org/content/10/426/eaan4488
> In situ vaccination with low doses of TLR ligands and anti-OX40 antibodies can cure widespread cancers in preclinical models.
Woha, I had no idea that we can genetically engineer animals to develop cancer. That is impressive, and a little scary...
Hmmm, not sure keeping the biopsy cells viable until biopsy results arrive though would be practical.
It's also not clear what toxicities were incurred with this therapy (in mice), which is a significant concern for the approval of any drug in humans.
Do not get your hopes up just yet.
Why would that be the case?
If you want something to get your hopes up, look for stuff undergoing human studies. They're not new(s) -- in fact, it's stuff that is known and has shown promise for years -- but they're more likely to eventually work.
The point of the butterfly effect is that everything you do could be responsible for some massive change in the future. (though the odds are extremely low)
"using this treatment" and "not using this treatment" are about equally likely to cause a butterfly effect.